Method of measuring cardiac related parameters non-invasively via the lung during spontaneous and controlled ventilation

ABSTRACT

An apparatus to measure cardiac output (Q) and other parameters such as alveolar ventilation (VA), minute CO 2  elimination from the lung (VCO 2  ), minute oxygen consumption (VO 2 ), oxygenated mixed venous partial pressure of CO 2 , (PvCO 2 -oxy), true mixed venous partial pressure of CO 2 (PvCO 2 ), PaCO 2 , mixed venous oxygen saturation (SvO 2 ), pulmonary shunt, and anatomical dead space, consisting of: a) a breathing circuit with characteristics that: i. on exhalation, exhaled gas is kept substantially separate from inhaled gas; ii. oninhalation, when V E  is greater than FGS flow, the subject inhales FGS first and then inhales a gas that is substantially SGS, for the balance of inhalation; b) gas sensor means for monitoring gas concentrations at the patient-circuit interface c) a first gas set (FGS), and a second gas set (SGS), said second gas set which may comprise previously exhaled gases or exogenous gases or both d) a gas flow control means for controlling the rate of FGS flow into the breathing circuit e) means to identify phase of breathing, said means may consist of pressure sensors or analysis of signal generated by gas sensors or other means known to those skilled in the art; f) machine intelligence consisting of a computer or logic circuit capable of controlling the gas flow control means, receiving the output of the gas sensor means and means to identify phased of breathing, and performing the calculations for measuring cardiac output and other parameters as outlined in the disclosure.

FIELD OF THE INVENTION

This invention discloses a method that calculates noninvasively, via the lung, the total cardiac output, pulmonary blood flow, shunt flow, anatomical and alveolar deadspace, true mixed venous O₂ saturation, true mixed venous PCO₂, and PaCO₂. Furthermore the method can be performed in ventilated subjects, subjects breathing spontaneously, even in the presence of variations in their tidal volume and breathing frequency. Subjects need not perform any respiratory manoeuvre such as hyperventilation or breath holding to perform the test.

BACKGROUND OF TE INVENTION

1. Importance of Cardiac Output

A physician's ability to determine a patient's cardiac output ({dot over (Q)}, the volume of blood pumped by the heart each minute) is important in the assessment of critically ill patients. There are various devices and methods that provide a direct or indirect measure of {dot over (Q)} (see table 1). The most common method used in clinical practice is thermo-dilution, established by Ganz et al (1). Commercially manufactured catheters (referred to as Swan-Ganz catheters, named after the inventors) contain multiple lumina, an embedded thermister, and a balloon at the tip. The method requires the insertion of the catheter through the skin to access a large central vein such as the internal jugular, subclavian, cephalic or femoral. When the balloon at the end of the catheter is inflated, the catheter tip is carried along with the flow of blood to the right ventricle of the heart and then into the pulmonary artery. The part of the catheter that remains outside the body has connections that can be attached to electrical sensors that determine the pressure and temperature in the pulmonary artery where the tip of the catheter is positioned. Calculation of {dot over (Q)} requires the injection of a fixed volume of cool liquid of known temperature into a lumen of the catheter that has its opening part way along its length (usually in a part of the catheter in the right atrium). The thermister at the tip of the catheter will register changes in temperature as the cool liquid, carried by the blood, passes. The extent of dilution of the cold bolus of liquid by warm blood will determine the temporal profile of the temperature change at the tip of the catheter. This is referred to as the thermodilution method of measuring cardiac output(TD{dot over (Q)}).

The popularity of TD{dot over (Q)} stems from ease of use once the catheter is in place. However, the placing and maintenance of the catheter entails considerable risk and expense. Insertion of the Swan-Ganz catheter is associated with complications that are frequently fatal such as puncture of the carotid or subdavian artery with associated internal haemorrhage or stroke, tension pneumothorax, rupture of the right ventricle, malignant arrhythmias (including fatal ventricular fibrillation), and rupture of the pulmonary artery. As a foreign body violating the skin barrier, a pulmonary artery catheter is a constant threat as a source of blood-born infection that is the greatest risk to heart valves, artificial joints, and other implants. Such infections are medical disasters leading to severe morbidity and death. Furthermore, the use of pulmonary artery catheters to measure TD{dot over (Q)} is very expensive as it requires admission to an intensive care facility where there is continuous presence of critical care nursing and medical staff. Despite these risks, it is still not the ideal method to measure {dot over (Q)} as it tends to overestimate {dot over (Q)} by as much as 10% compared to the Fick method (see below) and, for greatest accuracy, requires repeated measurements as its precision is poor. The variability of repeated single measurements is about 22% and can be reduced to 10% by repeated averages of 3 measurements (2). A single thermodilution measurement is considered to be plus or minus 33% the true value.(3)

Because of the expense and risks of keeping the catheters in place, they are removed as soon as practical, often within 24-48 hours of major heart surgery. Often they are removed while the information they provide can still be clinically useful and well before the patient is no longer at significant risk for relapse. If the patient's health deteriorates, a decision must be made about re-inserting the catheter.

An automated non-invasive method of {dot over (Q)} monitoring would be very useful in the following clinical scenarios:

-   -   a) Selected low risk patients now routinely undergoing pulmonary         artery catheterization for intra- and postoperative monitoring.     -   b) Patients whose {dot over (Q)} would be clinically important         to know but in whom the risks and costs of insertion of a         pulmonary catheter cannot be justified; this includes ward         patients, outpatients or patients in the emergency department or         doctor's office.     -   c) Patients who are too sick to warrant the added risk of         pulmonary artery catheter insertion     -   d) High and moderate cardiac risk patients undergoing minor and         moderate non-cardiac surgical procedures     -   e) Severely ill patients with non-cardiac disease.     -   f) Relatively healthy patients undergoing major stressful         surgery.     -   g) Situations in which {dot over (Q)} is clinically indicated         but there is no access to the expertise and critical care         facilities required for the use of the pulmonary artery         catheters.     -   h) Means of monitoring response to cardiovascular therapy such         as for hypertension and heart failure.     -   i) As a non-invasive diagnostic test of cardiopulmonary status.     -   j) As a means of assessing cardiovascular fitness.

Despite these many applications, non-invasive methods of {dot over (Q)} measurements have not obtained widespread clinical acceptance. The most commonly researched methods include ECG bio-impedance (Imhoff, 2000 (4)), and pulsed-wave Doppler esophageal sonography. These methods have good repeatability (5-12) and good limits of agreement with either thermodilution or Fick-based methods but only in some populations of subjects. Each method fails in certain patients groups with such pathologies as very high or low {dot over (Q)} states as occur in surgical patients, septic shock, exercise or cardiogenic shock.

2. Background Physiology and Definition of Terms

Venous blood returns to the right side of the heart from the muscles and organs with reduced oxygen (O₂) and increased carbon dioxide (CO₂) levels. Blood from various parts of the body is mixed in the right side of the heart and pumped to the lungs via the pulmonary artery. The blood in the pulmonary artery is known as the mixed venous blood. In the lungs the blood vessels break up into a network of small vessels that surround tiny lung sacs known as alveoli. This network of vessels surrounding the alveoli provides a large surface area for the exchange of gases by diffusion along their partial pressure gradients. After a breath of air is inhaled into the lungs, it dilutes the CO₂ left in the alveoli at the end of the previous expiration, thereby establishing a pressure gradient between the partial pressure of CO₂ (PCO₂) in the mixed venous blood (P vCO₂) arriving at the alveoli and the alveolar PCO₂ (PACO₂). The CO₂ diffuses into the alveoli from the mixed venous blood diminishing the PCO₂ in the blood, and increasing the PCO₂ in the alveoli until equilibrium is established between the PCO₂ in alveolar capillary blood and the PCO₂ in the alveoli. The blood then returns to the left side of the heart via the pulmonary vein and is pumped into the arterial system by the left ventricle. The PCO₂ in the arterial blood (PaCO₂) is now the same as that in the alveoli. When the subject exhales, the gas at the very end of exhalation is considered to have come from the alveoli and thus simultaneously reflects the PCO₂ in the pulmonary capillaries and the alveoli; the PCO₂ in this gas is called the end-tidal PCO₂ (PETCO₂).

The volume of gas breathed per minute, or minute ventilation ({dot over (V)}E), is measured at the airway opening (nose and/mouth) and is expressed in L/min. The volume of breathed gas distributed to the alveoli (and thus contributing to gas exchange) is termed the alveolar ventilation ({dot over (V)}A) and is also expressed in L/min. The part of {dot over (V)}E that does not contribute to gas exchange is termed dead space ventilation. This is divided into the anatomical dead space that consists of the trachea and other gas-conducting tubes leading from the nose and mouth to the alveoli, and the alveolar dead space that is collectively the alveoli that are ventilated but not perfused with blood.

The {dot over (V)}E during normal breathmng provides the {dot over (V)}A that is required to eliminate the CO₂ brought to the lungs. {dot over (V)}E is controlled by a feedback system to keep PaCO₂ at a set level of approximately 40 mmHg. Under steady state conditions, the rate at which CO₂ is exhaled from the lungs ({dot over (V)}CO₂) is equal to the rate that it is brought to the lungs, which in turn is equal to the metabolic CO₂ production. We define steady state as the condition in which the flux of CO₂ at the lungs is equal to the CO₂ production and the {dot over (V)}CO₂, P vCO₂ and PaCO2 remain steady. If the {dot over (V)}CO₂ is diminished, the CO₂ extraction from the mixed venous blood passing by the alveoli will be reduced resulting in an increase in the PaCO₂ when that blood reaches the arterial system. As the blood traverses the body, it will pick up additional CO₂ and will return to the pulmonary artery with a higher PCO₂ than on its previous passage. The time between the change in {dot over (V)}CO₂ and re reappearance of the blood with raised PCO₂ in the mixed venous circulation is termed the recirculation time which is generally taken as 20-30 s in resting subjects.

3. The Fick Equation

The approach for respiratory-based methods for measuring {dot over (Q)} non-invasively is described by the Fick equation, a mass balance of any substance across the lungs. The Fick method was originally described for O₂ as a method for determining pulmonary blood flow. The Fick relation states that the O₂ uptake by the lung is equal to the difference between the pulmonary artery and systemic arterial O₂ contents times the {dot over (Q)}. The blood contents originally had to be obtained invasively from blood samples. The same relation holds with respect to CO₂. The advantage of using CO₂ as the tracer is that mixed venous and arterial blood contents of CO₂ may be determined non-invasively. The Fick mass balance equation for CO₂ is: $\overset{.}{Q} = \frac{\overset{.}{V}\quad{CO}_{2}}{\left( {{C\overset{\_}{v}{CO}_{2}} - {{Ca}{CO}}_{2}} \right)}$ where {dot over (Q)} is the cardiac output, {dot over (V)}CO₂ is the rate of elimination of CO₂ at the lungs, C vCO₂ and CaCO₂ are the mixed venous and systemic arterial contents of CO₂, respectively. {dot over (V)}CO₂ can be measured by a timed collection of expired gas and measuring its volume and CO₂ concentration. The term CaCO₂ can be calculated using an estimate of arterial PCO₂ (PaCO₂) as derived from the PCO₂ of end tidal gas (PETCO₂). The hemoglobin concentration (easily obtained from a venous blood sample or a drop of blood from a finger prick) and the relation between blood PCO₂ and CO₂ content (available from standard physiology texts) are then used to calculate CaCO₂.

However, C vCO₂ is difficult to estimate. The PCO₂ of mixed venous blood (P vCO₂) is difficult to determine as true mixed venous blood is present only in the pulmonary artery, which is inaccessible from the surface. The air in the lungs is in intimate contact with mixed venous blood, but CO₂ diffuses rapidly from the mixed venous blood into the alveoli before an equilibrium is established. The PCO₂ of the expired gas therefore reflects this equilibrium PCO₂ and not the PCO₂ of mixed venous blood. The P vCO₂ can be determined from expired gas only when there has been full equilibration with continuously replenished mixed venous blood or partial equilibration under controlled conditions that allow for back calculation of P vCO₂ from the PCO₂ in expired gas. Hence during rebreathing, the alveolar gas is not refreshed and the mixed venous blood continuously passes the alveoli such that an equilibrium is established whereby the PETCO₂ reflects the PCO₂ in mixed venous blood.

However, even in this scenario, the PCO₂ is not that which exists in the pulmonary artery. Blood in the pulmonary artery has a relatively low PO₂. Because of the Haldane effect, the low PO₂ allows the CO₂ to be carried by the hemoglobin at a relatively low PCO₂. When the mixed venous blood is exposed to gas in the alveoli, O₂ diffuses into the blood, binds to the hemoglobin and increases the PCO₂ needed for a given CO₂ content on the hemoglobin (the complimentary aspect of the Haldane effect). All methods based on full or partial equilibration of alveolar gas with P vCO₂ take into account that the equilibration is to a virtual PCO₂ that would exist if the CO₂ content of the hemoglobin were the same as in mixed venous blood but the hemoglobin were saturated with O₂. We refer to this as the oxygenated mixed venous PCO₂ (P vCO-oxy). Because the relationship between PCO₂ and content of CO₂ in blood is known, C vCO₂ can be calculated from both the true P vCO₂ (as obtained, for example, from a pulmonary arterial blood sample) and P vCO₂-oxy (as obtained by some of the non-invasive methods described below)¹. ¹ The Pv CO₂-oxy does not really exist but is a virtual number created by instantaneously oxygenating mixed venous blood before and diffusion of CO₂ into the alveoli. The C vCO₂ is the same in each.

4. Rebreathing—Equilibration Method

One method of measuring P vCO₂-oxy was introduced by Collier in 1956, and is known as the equilibration method. A bag is pre-filled with a high concentration of CO₂ (˜10-13%) and the subject exhales and inhales rapidly to and from the bag and PCO₂ is monitored continuously at the mouth. The object of the test is to find the combination of bag volume and bag concentration of CO₂ such that once the gas in the bag mixes with that in the lungs (the concentration of CO₂ in the residual gas in the lung at the end of a breath in a healthy person is ˜5.5%), the partial pressure of CO₂ in the lung is equal to that in mixed venous blood. A flat segment of the PCO₂ tracing segment indicates that inspired and expired PCO₂ are equal. To identify the true P vCO₂-oxy, the flat segment must occur within the first 3-4 breaths, before recirculation raises the P vCO₂-oxy (see FIG. 8).

-   -   4.1.1 Advantages of the Equilibration Method:

The capnograph reading is of gas equilibrated with P vCO₂-oxy and can be considered a directly measured value as opposed to a value obtained from calculation or extrapolation.

-   -   4.1.2 Limitations of the Equilibration Method:         -   4.1.2.1 The CO₂ concentration in the bag depends on bag             size, the patient's lung volume, and the P vCO2-oxy—the last             being the unknown value. Therefore, the concentration of CO₂             in the bag must be individualized to the patient and thus             found by trial and error. The method is therefore difficult             to automate fully.         -   4.1.2.2 In practice, since the characteristic of a suitable             endpoint (the plateau of PCO₂) is subjective, identification             of a suitable plateau is difficult to automate.         -   4.1.2.3 The manoeuvre of rebreathing from a bag is difficult             to perform in mechanically ventilated patients and is             therefore not suitable for such patients.         -   4.1.2.4 Inhaling 10-13% CO₂ is very uncomfortable and most             people cannot tolerate it It is particularly uncomfortable             to someone who is short of breath or exercising.         -   4.1.2.5 The method requires an external source of CO₂. This             makes testing equipment bulky and awkward.         -   4.1.2.6 The method requires that the subject hyperventilate             in order to mix thoroughly the gas in the bag and the lungs             before recirculation of blood takes place. This requirement             limits the test to those subjects who can perform this             manoeuvre and who can provide this degree of cooperation.             This excludes patients who have severe lung disease, those             who are too young, too confused or too ill to cooperate.         -   4.1.2.7 The test loads a considerable volume of CO₂ into the             subject's lungs and at the same time prevents CO₂ from             leaving the blood for the duration of the test This has             negative consequences for the subject:             -   4.1.2.7.1 Following the test, the subject must                 hyperventilate to eliminate the applied CO₂ load as well                 as the volume of metabolically-produced CO₂ not                 eliminated during the test. This may pose a considerable                 burden for some subjects with lung disease or exercising                 subjects who are already expending considerable effort                 to cope with their existing metabolic CO₂ load.             -   4.1.2.7.2 A period of hyperventilation following the                 test is required to eliminate the CO₂. This may be                 difficult for some subjects to perform and,                 consequently, they may experience respiratory distress                 for some time until their PCO₂ is decreased.             -   4.1.2.7.3 Repeated tests must be delayed until the extra                 CO₂ is eliminated and the baseline state re-established.             -   4.1.2.7.4 The test itself may distress the subject and                 alter the {dot over (Q)}.

5. Rebreathing—Exponential Method

In this technique, a small amount of CO₂ is placed in a bag and the subject asked to rebreathe from the bag. The PETCO₂s of successive breaths will rise exponentially towards P vCO₂-oxy. A rising exponential curve is then fit to the PETCO₂s of these breaths to predict an asymptotic value that is assumed to be the P vCO₂-oxy (See FIG. 9).

5.1 Advantages of the Exponential Method

-   -   5.1.1 There is no requirement for respiratory manoeuvres by the         patient     -   5.1.2 A smaller CO₂ load is placed on the subject in order to         perform the test.

5.2 Limitations of the Exponential Method

-   -   5.2.1 This is an indirect test in which the P vCO₂-oxy is not         measured directly but calculated from data generated by a test     -   5.2.2 As the metabolic production of CO₂ is small compared to         the size of the lung and bag, the rise of PCO₂ occurs over a         prolonged period. This severely limits the number of useful data         points for accurate extrapolation from an exponential curve,         before recirculation     -   5.2.3 The most important limitation of this and other methods         that use partial equilibration during rebreathing to extrapolate         to an asymptote using a single exponential is that the         assumptions underlying the method are incorrect. In fact, the         method produces two different mathematical profiles: the one         describing the washout of CO₂ from the lung into the bag is a         decreasing exponential whereas the second describing the         build-up of CO₂ released from the blood into the lung-bag         mixture is an increasing exponential (13). Only after the gases         in the lung-bag system have become well mixed do the two         exponentials resolve to a single exponential. By then, very few         breaths (if any) that can provide suitable data for         extrapolation from a single exponential can be taken before         recirculation.     -   5.2.4 A continually rising level of CO₂ makes this test         unpleasant in conscious patients, especially in those exercising         or very ill.     -   5.2.5 The manoeuvre of rebreathing from a bag is difficult to         perform in mechanically ventilated patients and is therefore not         suitable for such patients.     -   5.2.6 The method requires an external source of CO₂. This makes         testing equipment bulky and awkward.     -   5.2.7 The test loads a volume of CO₂ into the subject's lungs         and at the same time prevents CO₂ from leaving the blood for the         duration of the test Although the extent of the CO₂ load on the         subject is less than with the equilibration method, the negative         consequences for the subject, outlined in the section on the         equilibration method discussed above, must be considered.     -   5.2.8 Priming the rebreathing bag with some CO₂ improves the         predictive qualities of the asymptote since every data point         lies closer to the asymptote, but the increased CO₂         concentrations increase the discomfort and the limitations         approach those outlined above for the equilibration method.

6.0 Calculating {dot over (Q)} without First Ccalculating P vCO₂-oxy

Gedeon in 1980 described a method of calculating {dot over (Q)} in ventilated patients via a differential Fick method that circumvents the need to calculate P vCO₂-oxy. The underlying assumptions of the method are that {dot over (Q)} and P vCO₂ will remain unchanged during a step change in lung CO₂ elimination and alveolar PCO₂ (PACO₂) lasting less than a recirculation time (about 30 seconds). Gedeon proposed reducing lung CO₂ elimination by reducing either the tidal volume or respiratory frequency setting of the ventilator. As a modification of this method, Orr et al. proposed leaving the ventilator settings unchanged and reducing lung CO₂ elimination by temporarily interposing a dead space between the ventilator and the patient's airway resulting in a transient period of rebreathing previously exhaled gas.

6.1 Theoretical Basis of Gedeon/Orr Method:

The method applies to a subject being ventilated under control conditions in which CO₂ elimination and PETCO₂ are measured. A test manoeuvre consisting of a transient alteration in the CO₂ elimination for a time less than a recirculation time is effected and the resulting “equilibrium” PETCO₂ is noted. It is assumed that the {dot over (Q)} and P vCO₂-oxy during the test are unchanged from control conditions. The Fick equation for these two conditions can be written as $\overset{.}{Q} = \frac{\overset{.}{V}\quad{CO}_{2}}{{C\overset{\_}{v}{CO}_{2}} - {{Ca}{CO}}_{2}}$ $\overset{.}{Q} = \frac{\overset{.}{V}\quad{CO}_{2}^{\prime}}{{C\overset{\_}{v}{CO}_{2}} - {{Ca}{CO}}_{2}^{\prime}}$ where {dot over (V)}CO₂′ is the CO₂ flux at the lungs during the test and CaCO₂′ is the corresponding ‘new’ arterial content of CO₂. These two equations can be combined to yield the differential form of Fick's equation: $\overset{.}{Q} = \frac{\Delta\quad\overset{.}{V}\quad{CO}_{2}}{\Delta\quad{{Ca}{CO}}_{2}}$ where Δ denotes a “difference in”. Since the PaCO₂ and P vCO₂-oxy lie on the same CO₂ dissociation curve, partial pressures of CO₂ can be substituted for CO₂ content to yield the following relation: $\overset{.}{Q} = \frac{\Delta\quad\overset{.}{V}{CO}_{2}}{S*\Delta\quad{{Pa}{CO}}_{2}}$ where S is the slope of the CO₂ dissociation curve. like the conventional non-invasive CO₂-based Fick method, the differential Fick method relies on predicting PaCO₂ through measurements of PETCO₂. However, instead of requiring a calculation of P vCO₂-oxy, the differential Fick equation assumes no change in P vCO₂-oxy over the duration of the test, and uses the measured quantities {dot over (V)}CO₂ and {dot over (V)}CO₂′ and well as PaCO₂ and PaCO₂′ (from PETCO₂) to calculate the remaining unknown value in the equation: {dot over (Q)}.

6.2Advantages of Gedeon/Orr Method

-   -   6.2.1 The main advantage is that P vCO₂ does not need to be         calculated.     -   6.2.2 If the deadspace method is used to alter the {dot over         (V)}CO₂, then no change in breathing pattern is required.     -   6.2.3 The method can, theoretically, be fully automated. (In its         present commercial form, the size of the interposed deadspace         must still be altered manually).

6.3 Limitations of Gedeon/Orr Method

There are a number of limitations in applying Orr's method to spontaneously ventilating subjects.

-   -   6.3.1 In spontaneously breathing subjects, there is considerable         breath-to-breath variation in breath size and breathing         frequency resulting in a variation in PETCO₂. This poses         problems with respect to:         -   6.3.1.1 Identification of PETCO₂ and PETCO₂′. Long periods             of baseline measurements are needed in order to average the             end tidal values and identify the PETCO₂ to be used as the             baseline PETCO₂ in the differential Fick equation. The test             phase cannot last for more than about 30 seconds (due to             recirculation), typically 5 breaths. This leaves little time             to deternine an accurate average PETCO₂′. During prolonged             baseline periods of observation, the condition of the             patient may change.         -   6.3.1.2 Calculation of {dot over (V)}CO₂. The variations in             PETCO₂ are related to variations in CO₂ elimination but the             relationship is not consistently reflected by the PETCO₂.             For example, assuming a subject breathing at rest with an             average resting breath size, an interposed smaller breath             may result in a lower PETCO₂ (due to a smaller contribution             of alveolar gas to the end tidal sample) but the CO₂             elimination from that breath will be diminished. Conversely,             a larger breath may result in the same PETCO₂ as the resting             breath but a greater volume of CO₂ is eliminated. The             commercial automated Gedeon method (NICO2, Novametrics             Medical Systems, Wallingford, Conn., U.S.A.) measures the             CO₂ eliminated breath-by-breath and therefore must             continuously average the values to measure {dot over             (V)}CO₂. The NICO2 method of calculating {dot over (V)}CO₂             by real-time integration of continuous measurements of flow             (with a pneumotachymeter) and CO₂ concentration (with a             capnograph) is fraught with potential for errors: a small             error in the integration of these two signals with different             time delays and time constants results in a much larger             error in the calculation of {dot over (V)}CO₂. In addition,             the greater the variability of the breath size and CO₂             concentrations, the longer the measurement time required for             an accurate estimate of {dot over (V)}CO₂.     -   6.3.2 Calculation of {dot over (V)}CO₂′. Stable transient         changes in {dot over (V)}CO₂ cannot be achieved in conscious         spontaneously ventilating patients:         -   6.3.2.1 Interposing a deadspace and raising their PCO₂ will             stimulate spontaneously breathing conscious subjects to             increase their {dot over (V)}E and {dot over (V)}CO₂ until             the PETCO₂ is restored.         -   6.3.2.2 Any change in breath size or frequency during a             period of breathing, (a normal occurrence in spontaneously             breathing people) changes the {dot over (V)}CO₂ during that             period. During inspiration, the deadspace gas is inhaled             first followed by fresh gas. A decrease in a breath size or             frequency diminishes the volume of fresh gas inhaled (and             thus the {dot over (V)}CO₂for that breath). An increase in             breath size or frequency will result in an increased volume             of fresh gas delivered to the alveoli.         -   6.3.2.3 Each breath is an independent event and there is no             inherent method to compensate in a subsequent breath for             changes in {dot over (V)}CO₂ in the preceding breath. For             the method to be implemented, therefore, measures must be             taken to ensure that breath size and frequency stay             absolutely constant during the test. The NICO₂ method has no             such built-in aspects. The method can therefore be used only             in patients who have precisely uniform breathing pattern             such as those that are paralysed and mechanically             ventilated.     -   6.3.3 Identification of PETCO₂-PaCO₂ gradient. The Gedeon and         Orr methods assume, or require the establishment of, a constant         gradient between the PETCO₂ and the PaCO₂. The variation in         PETCO₂ is due to variations of distribution of fresh gas to         various parts of the lung and any one breath does not reflect         the overall state of CO₂ exchange. On the other hand, such         variations are not reflected in the PaCO₂ which does reflect the         overall exchange of CO₂ and remains relatively constant.         Therefore, variations in PETCO₂ also confound the quantification         of the PETCO₂-PaCO₂ gradient under control conditions. Although         Orr provides a number of equations to correct for these         limitations, these equations are empirical and do not         necessarily apply to a particular patient. For example, they are         applied whether or not there is irregular breathing.

The PETCO₂ -PaCO₂ gradient during the test phase when rebreathing occurs is unknown. In the presence of large alveolar deadspace (as commonly occurs in many ill patients) the PETCO₂-PaCO₂ gradient will change during the rebreathing phase. Orr provides some equations to correct for this but since the volume of the alveolar deadspace is unknown, the applicability of the formula to any particular patient is unknown. This further diminishes the accuracy of calculating PaCO₂′.

The manoeuvres required to determine each of the terms required to calculate {dot over (Q)} ({dot over (V)}CO₂, {dot over (V)}CO₂′, PETCO₂, PETCO₂′ and PaCO₂′) by the Orr/Gedeon/NICO2 method is awkward to implement and prone to errors in measurement in the presence of any variation in breath amplitude or breathing frequency as occurs in spontaneously breathing humans or animals.

-   -   6.3.4 The parameter calculated by the differential Fick method         as practiced by Gedeon/Orr/Respironics is pulmonary blood flow         ({dot over (Q)}p). Pulmonary blood flow may be less than the         total cardiac output ({dot over (Q)}t) when, for example, some         of the {dot over (Q)} is shunted from the right side of the         circulation (superior vena cava, right atrium, right ventricle,         pulmonary artery) into the left side of the circulation without         passing through the lungs. This is referred to as “shunt” ({dot         over (Q)}s). About 5% of venous blood bypasses the lungs (termed         shunted blood) in healthy adults. Much larger shunts occur in         many medical conditions such as congenital heart disease,         surgical repair of some congenital heart diseases, pneumonia,         pulmonary edema, asthma, pulmonary atelectasis, adult         respiratory distress syndrome, obesity, pregnancy, liver disease         and others. The differential Fick method does not include         shunted blood in the calculation of {dot over (Q)} and other         empiric corrections must be made to account for it.

7.0 Kim-Rahn Farhi Method

7.1 Theory:

A unique maneuver was proposed by Kim, Rahn and Farhi, (J. Appl. Physiol. 21:1388-44. 1966.) as a way to calculate the oxygenated mixed venous PCO₂ (P vCO₂-oxy) as well as the true P vCO₂ and PaCO₂. It is based on a paradigm of taking a breath of O₂, holding the breath, and exhaling slowly over a period equal to the recirculation time. Over this time of exhalation, the CO₂ from the mixed venous blood will diffuse into the alveoli and O₂ will be absorbed. The low PO₂ in the red blood cells in the mixed venous blood maximizes the volume of CO₂ that can be carried by hemoglobin. Oxygen from the alveoli diffuses into the red blood cells, raising the PO₂ and decreasing the affinity of hemoglobin for CO₂ (Haldane effect). This releases CO₂ from the binding sites on the hemoglobin, making it available for diffusion into the alveoli. With breath holding, CO₂ will accumulate in the alveoli and the alveolar PCO₂ (PACO₂) will rise until it no longer provides a gradient for diffusion from the blood. (This PCO₂ is known as the oxygenated mixed venous PCO₂ (P vCO₂-oxy).) However, O₂ will continue to diffuse as long as the PAO₂ is greater than P vO₂. Relatively little CO₂ need diffuse into the alveoli to reach P vCO₂-oxy compared to the volume of O₂ that is available for uptake before the PO₂ in the pulmonary capillary blood is in equilibrium with the PAO₂. In other words, the equilibration of CO₂ in the alveoli with the mixed venous blood will occur well before that of O₂.

Since both O₂ and CO₂ are contained in the same physical volume, the changes in concentrations of each gas over a short period will reflect the rates of flux of that gas over the same period. Therefore, over a short period, the ratio of PCO₂ to PO₂will reflect the respiratory quotient, RQ (defined as the rate of CO₂ diffusion from the blood into the alveoli divided by the rate of O₂ absorption into the blood from the alveoli). The RQ will initially be highest at the beginning of the breath when the rate of CO₂ diffusion into the alveoli is maximal, and will approach 0 when the alveolar PCO₂ equals P vCO₂-oxy. In vitro studies have shown that PACO₂ equals the true P vCO₂ when the RQ=0.32 and equals PaCO₂ when RQ is equal to the patient's steady state RQ (typically ˜0.8).

7.2 Test Method

The method suggested for performing this test would require a subject to take a maximum breath of 100% O₂ and exhale very slowly and maximally. Over the course of this exhalation, expired gas is sampled and analyzed continuously for both PO₂ and PCO₂. PO₂ is graphed vs. PCO₂ and the RQ is calculated from the instantaneous slope of tangents to the curves at various PCO₂ values as follows: ${RQ} = \frac{{slope} - \left( {{FeO}_{2}*{slope}} \right) - {FeCO}_{2}}{1 - \left( {{FeO}_{2}*{slope}} \right) - {FeCO}_{2}}$

These RQ values are then plotted against their respective PCO₂ data points resulting in a linear relation as illustrated in FIGS. 4 and 5 of T. S. Kin, H. Rahn, and L. E. Farhi cited above.

7.3 Advantages of the Method.

-   -   7.3.1 This is the only known non-invasive method by which true P         vCO₂ can be calculated.     -   7.3.2 The method provides an estimate of PaCO₂ not based on         assuming a gradient between PETCO₂ and PaCO₂.     -   7.3.3 Data generated by the method can be used to calculate the         O₂ saturation of mixed venous blood.

7.4 Limitations of the Kim-Rahn-Farhi Breath-Hold Method.

The main limitation of this method is that it requires the subject to have a large lung capacity, hold his breath, and exhale over a prolonged duration. Patients with conditions such as pulmonary fibrosis, pneumonia, adult respiratory distress syndrome, chronic obstructive lung disease, asthma, obesity, trauma, abdominal and chest surgery, mental obtundation, confusion, pregnancy and many others have marked limitations in their ability to take a large breath Patients are required to cooperate with their duration of breath holding and rate of exhalation. Many patients who are ill, exercising subjects, children and others are unable to perform this satisfactorily. This method is very awkward to automate or perform on ventilated patients.

8.0 Fisher Method

8.1 Theory

In a steady state, if a subject breathes in a PCO₂ equal to P vCO₂-oxy, there will be no gradient for gas exchange and the difference in PCO₂ between the inspired PCO₂ (PICO₂) and the expired PCO₂ (PECO₂) will be 0. The volume of CO₂ diffusing into the alveoli will be maximal when the difference between PICO₂ and PECO₂ is greatest, i.e., when the PICO₂ is 0. Since the change in alveolar PCO₂ (PACO₂) varies directly as the volume of CO₂ diffusing into the alveoli and the volume diffusing into the alveoli varies directly as the gradient, then the difference between the PICO₂ and PECO₂ will vary inversely as PICO₂. In other words, graphing the difference between the PECO₂ and PICO₂ (PECO₂−PICO₂) vs. FICO₂ will result in a straight line. Since subjects normally breathe room air (PICO₂ equals 0 or O₂ the control PETCO₂ provides the first point on the graph. When subjects inhale gas with any constant value of PCO₂, the PETCO₂ at the end of an equilibration period not exceeding the time for recirculation will provide a second data point which can be used to define the straight line which crosses the X axis where PICO₂ equals P vCO₂-oxy.

8.2 Test Method:

The subject breathes via a non-rebreathing valve. The inspiratory limb is provided with either fresh gas or test gas with any PCO₂. To perform a test, the inspired gas is switched from control gas to test gas for about one recirculation time. The PICO₂ of the test gas, the PETCO₂ just before the test (when PICO₂ was 0), and the PETCO₂ of the last breath before recirculation are used to calculate the P vCO₂-oxy.

8.3 Advantages of the Prior Disclosed Previous Fisher Method:

-   -   8.3.1 Any low inspired concentration of CO₂ such as 1% is         adequate to generate a data point; therefore the subject need         not get a large CO₂ load.     -   8.3.2 This Fisher method extrapolates to the P vCO₂-oxy from a         linear function and is therefore easier to calculate and more         accurate than with the partial rebreathing test in which data         points are fit to an exponential curve for extrapolation to an         asymptote.     -   8.3.3 The PICO₂ can be any value, so accurate mixtures of gases         are not required.     -   8.3.4 Assuming arterial PCO₂ values (PaCO₂) can be obtained from         arterial blood sample, for example, the method measures total         {dot over (Q)}, not just pulmonary blood flow.     -   8.3.5 The subject need not carry out any respiratory manoeuvre         such as breath holding or hyperventilation.     -   8.3.6 The method does not entail any rebreathing. Therefore, O₂         levels remain stable throughout the test and supplemental O₂ is         not needed.

8.4 limitations of the Fisher Method.

-   -   8.4.1 Uniform breath size cannot be guaranteed in spontaneously         breathing subjects. A change of breath size or breathing         frequency during the latter parts of the test phase will affect         the PETCO₂ and thus the calculation of P vCO₂-oxy. Furthermore,         as the subjects are inhaling gas that contains CO₂, they may be         stimulated to take larger or more frequent breaths.     -   8.4.2 The test requires an external source of CO₂. This must be         supplied via a tank of CO₂ and a gas blender or via a tank of         premixed gas. If more than one test gas is required, then         arrangements to blend additional gases must be made or more than         one additional gas tank is required. This is inconvenient,         costly, and adds complexity to the test method and additional         bulk and weight to the test apparatus.     -   8.4.3 It is very complex to configure an automated system that         works for both spontaneously breathing and mechanically         ventilated patients.     -   8.4.4 There is no simple method to adapt currently available         ventilators, anaesthetic machines or breathing circuits to         provide a known and constant PICO₂ for a fixed number of         breaths.     -   8.4.5 The technique is difficult to adapt to anaesthetized         patients breathing via a circle circuit in which both the test         gas and the anaesthetic gases enter the circuit, especially in         the presence of a CO₂ absorber removing CO₂ from the circuit.

OBJECT OF THE INVENTION

It is therefore a primary object of this invention to provide an improved method and apparatus for the purpose of non-invasively determining cardiac output ({dot over (Q)}) which may be utilized in ventilated subjects, subjects who breath spontaneously or subjects who are under controlled ventilation such as those undergoing surgical procedures under general anesthesia.

It is yet a further object of this invention to provide an improved method and the apparatus related thereto for the purposes of non-invasively determining alveolar ventilation ({dot over (V)}A) and calculating minute CO₂ production ({dot over (V)}CO₂), oxygenated mixed venous PCO₂ (P vCO₂-oxy), true mixed venous PCO₂ ( true P vCO₂), pulmonary shunt, anatomical dead space, arterial PCO₂, at a greater accuracy than prior known non-invasive methods and apparatuses would provide.

It is yet another object of the invention to provide a method of non-invasively calculating the oxygen saturation of mixed venous blood (S vO₂) which may be utilized to reveal heart failure of septic shock in a patient or the like.

It is yet a further object of this invention to provide an improved method and the apparatus related thereto for the purposes of determining {dot over (Q)}, {dot over (V)}A and calculating {dot over (V)}CO₂, P vCO₂-oxy, true P vCO₂, pulmonary shunt, anatomical dead space in a non-invasive and fully automated manner.

Further and other objects of the invention will become apparent to those skilled in the art when considering the following summary of the invention and the more detailed description of the preferred embodiments illustrated herein.

SUMMARY OF THE INVENTION

This invention discloses a method and apparatus for calculating all of the {dot over (Q)} regardless of shunt, calculating the shunt, anatomical and alveolar deadspace, true mixed venous O₂ saturation, true mixed venous PCO₂, and PaCO₂. Furthermore the method and apparatus can be used with ventilated subjects, subjects breathing spontaneously, even with marked variations in their tidal volume and breathing frequency, or subjects undergoing surgery under anaesthesia. Subjects need not perform any respiratory manoeuvre such as hyperventilation or breath holding.

According to one aspect of the invention there is provided an improved method and apparatus for the purposes of determining {dot over (Q)} and {dot over (V)}A and calculating {dot over (V)}CO₂, P vCO₂-oxy, true P vCO₂, PaCO₂, pulmonary shunt, and anatomical dead space which increases the accuracy of these determinations in relation to known methods and apparatus and allows the full automation of the various methods disclosed herein for these determinations and calculations

The new method:

-   -   1. is insensitive to changes in minute ventilation ({dot over         (V)}E), tidal volume and/or respiratory frequency so that the         method can be carried out in spontaneously breathing subjects;     -   2. is simplified and less expensive to construct compared to         other non-invasive automated methods of performing the         differential Fick technique in that         -   a. it does not necessarily require any mechanically             activated valves to be actively engaged in the patient             circuit         -   b. does not require a pneumotachygraph to measure flows         -   c. does not require manual adjustment of an interposed dead             space (and thus can be totally automated);             -   d. The device will be the same for all sizes of adults                 (one size fits all)     -   3. is compatible with a number of sequential gas delivery         breathing (SGDB) circuits. A SGDB circuit provides for the         sequential delivery of two gas sets to the lungs during         inhalation. A gas set is composed of one or more gases and         vapors. The first gas set (FGS) is provided from the beginning         of inhalation and can terminate at some time during inhalation         depending on the FGS flow and the {dot over (V)}E, at which time         inhalation continues with the delivery of the second gas set         (SGS). For the purposes of measuring {dot over (Q)} and the         other physiologic parameters described herein, it is preferred         that there is a distinct transition from FGS to SGS and there is         no mixing of the gas sets. A small degree of mixing of FGS with         SGS during the latter part of inhalation will reduce accuracy of         the measured and calculated results. Mathematical corrections         can be made to minimize effect of the mixing of FGS with SGS,         but cannot completely negate the effects in all circumstances.         Therefore, breathing circuits which separate the FGS from the         SGS are preferred.     -   4. the generation and presentation of data will be substantially         the same for controlled (mechanical) ventilation and rebreathing         so that the algorithms to perform the tests and analyze the data         can be substantially the same;     -   5. can institute an equilibrium steady state within one         recirculation time so that the value for PETCO₂ will be a true         measured value rather than one requiring multiple corrections         based on unsubstantiated assumptions;     -   6. will allow the measurement of a new steady state PETCO₂         within one recirculation time and thus actualize the assumption         underlying the Differential Fick approach that P vCO₂ is         unchanged;     -   7. will minimize the effect of changes in tidal volume on the         alveolar ventilation.     -   8. maintain the alveolar PO₂ while maldng pulmonary blood flow         measurements;     -   9. make all calculations without a requirement to measure         breath-by-breath volumes of inspired and expired CO₂ or any         flows of tidal gases.

According to one aspect of the invention there is provided an improved apparatus and method of identifying the alveolar ventilation ({dot over (V)}A), substantially as illustrated and described herein, preferably the {dot over (V)}A so determined is utilized to calculate the {dot over (V)}CO₂ as {dot over (V)}A×FETCO₂. where FETCO₂ is the fractional pressure of CO₂ in end tidal gas.

In one embodiment of the improved apparatus and method:

-   -   a) the Fisher approach is used to determine P vCO₂-oxy (or)     -   b) the Kim Rahn Farhi approach is used to determine         -   i) P vCO₂-oxy         -   ii) true P vCO₂         -   iii) PaCO₂         -   iv) true P vCO₂ plus the information from a pulse oximeter             to determine mixed venous hemoglobin O₂ saturation (or)     -   c) the differential CO₂ Fick technique of Gedeon and Orr is         utilized to determine any combination of         -   i) P vCO₂-oxy         -   ii) {dot over (Q)}         -   iii) {dot over (V)}CO₂         -   iv) {dot over (V)}CO₂′         -   v) PETCO₂-PaCO₂ gradient determined using the PaCO₂ as             determined by the Kim Rahn Farhi method from data collected             while reducing the {dot over (V)}CO₂ in order to perform the             Differential Fick method. (or)     -   d) {dot over (Q)} is determined via the Kim Rahn Farhi method         performed during partial rebreathing using a CO₂ Fick method         where the         -   i) {dot over (V)}CO₂ is calculated with or without the new             method as disclosed         -   ii) CaCO₂ and C vCO₂ are determined from the PaCO₂ and P             vCO₂ respectively derived by the Kim Rahn Farhi method; (or)     -   e) calculation of the respiratory quotient (RQ) is determined as         PETCO₂/(PIO₂-PEO₂); (or)     -   f) PaCO₂ is determined directly via analysis of arterial blood         sample, arterialized venous sample, transcutaneous PCO₂         electrode, or other methods known to those skilled in the art.         wherein said apparatus or method may be utilized for very         accurate non-invasive determination of {dot over (Q)} and the         other indicated parameters.

According to yet another aspect of the invention there is provided an improved method of apparatus for determining {dot over (V)}A, {dot over (V)}CO₂ and calculating {dot over (Q)}, P vCO₂ - oxy, true P vCO₂, PaCO₂, pulmonary shunt, anatomical dead space, and O₂ saturation in mixed venous blood; which increases the accuracy of these determinations and calculations in relation to known methods and apparatuses and allows for full automation thereof if necessary by using automated means well known to those skilled in the art, to:

i) induce a step change in {dot over (V)}CO₂ by providing a step change in FGS flow to a SGDB circuit to create, with the control data at rest, two sets of data for said determination utilizing the differential Fick equations; (or)

-   -   ii) change the partial pressure of CO₂ in FGS of a SGDB circuit         to create, with the control data at rest, two sets of data for         said determination utilizing the Fisher or the differential Fick         equations; (or)     -   iii) change FGS flow or change the partial pressure of CO₂ in         FGS in a SGDB circuit to simulate complete or partial breath         holding and utilizing the Kim-Rahn-Farhi technique, wherein the         P_(ET)CO₂ of each breath is equivalent to a sequential alveolar         sample;         thereby providing more relevant data to calculate desired         parameters.

In yet another embodiment of the invention a ventilation circuit and method is provided for using sequential delivery of gas sets in order to identify the minute volume of gas entering the anatomical dead space and the minute volume entering the alveoli and thereby available for gas exchange ({dot over (V)}A). Subsequently, setting FGS flow to substantially equal to or less than {dot over (V)}A substantially controls {dot over (V)}A. A step reduction in {dot over (V)}A can then be induced by a step reduction in FGS flow, and resultant effects on end tidal gases such as CO₂ can be used in the to calculate {dot over (Q)} and other parameters as previously set out herein in the Background, disclosures and figures.

In yet another embodiment there is provided a method and apparatus of determining {dot over (Q)} and the other parameters disclosed by utilizing any SGDB circuit for example, the circuits described and illustrated herein by reducing the FGS flow to said circuit or increasing the PCO₂ of FGS to said circuit, independent of the breathing rate thereby allowing for calculations to be made via Differential Fick equations, and/or Fisher method, and/or the Kim-Rahn-Farhi method.

Preferably the method or apparatus previously described wherein the CO₂ content as calculated from P vCO₂-oxy and true P vCO₂ may be utilized to determine the O₂ saturation of mixed venous blood with known relations between CO₂ content, O₂ saturation and PCO₂.

In one embodiment the method or apparatus disclosed may be utilized wherein the arterial O₂ hemoglobin saturation, as determined by a non-invasive pulse oximeter, which makes the measurement by shining infrared light through a finger, is utilized with the O₂ saturation value in the pulmonary artery as calculated by the Kim Rahn Farhi method, to calculate the fraction of shunted blood (assuming fully oxygenated blood in the end pulmonary capillary) thereof.

Preferably said method or apparatus is utilized to determine the fraction of shunted blood {dot over (Q)}_(S), which in conjunction with determination of total cardiac output {dot over (Q)}_(T) (utilizing PaCO₂ as determined by the Kim Rahn Farhi method, or available from analysis or arterial blood or determined by transcutaneous PCO₂ determination or otherwise known to those skilled in the art, as a term in the Fick equation) and pulmonary blood flow {dot over (Q)}_(P) (utilizing PETCO₂ in the Fick equation) may be used to determine {dot over (Q)}_(S) the pulmonary output via the relationship. {dot over (Q)} _(S) ={dot over (Q)} _(T) −{dot over (Q)} _(P)

Preferably the method or apparatus disclosed wherein the O₂ saturation of haemoglobin in mixed venous blood (SaO₂), as determined therewith, is utilized to reveal a condition in a patient such as septic shock, or heart failure.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 8: PCO₂ vs time tracing during a rebreathing equilibrium test for determining oxygenated mixed venous PCO₂

FIG. 9: PCO₂ vs time tracing during exponential method of finding oxygenated mixed venous PCO₂.

FIG. 2 is a SGDB Circuit as taught by Fisher in U.S. Pat. No. 6,622,725 referred to herein as the Fisher circuit

FIG. 3 is similar to FIG. 2 wherein the reservoir bags are remote from the patient.

FIG. 5 is a new circuit for use with spontaneous ventilation.

FIG. 3B is similar to FIG. 5 wherein bypass limb, bypass valve, and passive expiratory valve are replaced by an active expiratory valve.

FIG. 3D is similar to FIG. 2 wherein an active valve has been added to the inspiratory limb to prevent mixing of FGS with SGS during inhalation

FIG. 5A is similar to FIG. 5 wherein an active valve has been added to the inspiratory limb to prevent mixing of FGS with SGS during inhalation.

FIG. 3E is similar to FIG. 2 wherein an active valve has replaced the passive inspiratory valve.

FIG. 5B is similar to FIG. 5 wherein an active valve has replaced the passive inspiratory valve.

FIG. 3C is similar to FIG. 3B wherein an active valve has replaced the passive inspiratory valve.

FIG. 4 shows a modification of any of the circuits shown in FIGS. 2, 3-3E, 5-5B for use with a mechanically ventilated patient.

FIG. 4B shows the preferred embodiment modified for use on ventilated patients.

FIG. 6 is a modification of the above circuits to include co-axially arranged inspiratory and expiratory limbs between the valves and the patient

FIG. 6A shows the preferred embodiment of the cardiac output circuit where inspiratory and expiratory limbs are co-axially arranged with the circuit of FIG. 5A.

FIG. 7 is a new circuit designed to allow measurement of cardiac output while delivering anesthetics or removing volatile agents from a patient

FIG. 5C shows a detail of a circuit design where the passive valves are surrounded by the exhaled gas reservoir

FIG. 10: Apparatus for non-invasive cardiac cardiac output apparatus consisting of a breathing circuit, gas sources, gas flow controllers, gas concentration sensors, and microprocessor capable of receiving and storing analog and digital input from sensors and operators, storing and following a decision tree, and generating output signals to a computer screen and to flow controllers.

FIG. 11 Flow diagram describing automated sequence of events performed by the non-invasive cardiac output apparatus in order to automatically generate and record data non-invasively and calculate {dot over (Q)} and other physiologic parameters.

FIG. 12 is a schematic of a standard anesthetic circle system herein provided as reference for discussion of disclosed system. Gas entering the anesthetic circuit consisting of oxygen, with the possible addition of air and/or nitrous oxide (N₂O), and possibly an anesthetic vapor such as isoflurane, desflurane or sevoflurane enters the fresh gas port (6) at a constant and known flow. The gas concentrations entering the circuit are set by the anesthesiologist The patient inspires through the patient port (1) and draws fresh gas plus gas drawn from the gas reservoir bag (4) through the CO₂ absorber (5) up the inspiratory limb (8). During exhalation, the inspiratory valve (7) closes and the fresh gas passes through the CO₂ absorber (5) towards the gas reservoir bag. Expired gas flows down the expiratory limb (2) displacing gas into the gas reservoir bag (4). When the reservoir bag is full, the pressure in the circuit rises, opening the APL (airway presslure relief) valve (9), and the rest of the expired gas exits the circuit through the APL valve. Gas is sampled continuously at the patient port and is analyzed for concentrations of constituent gases. The inspiratory (2) and expiratory (8) limbs consist of tubing (T).

FIG. 13 A detail of the computer screen output of an automated analysis of test finding {dot over (V)}A by progressive reduction in SGF flow method in a subject is illustrated in FIG. 13. The figure illustrates that progressive reduction of SGF (labelled “FGF” in the figure) results in a distinct inflection point when either PETCO₂ or PETO₂ is graphed as a function of SGF.

DETAILED DESCRIPITION OF THE INVENTION

Detailed Description of the Apparatus

Referring now to Figure ??, an apparatus is shown with the following components:

-   -   1) a breathing circuit (202), said breathing circuit preferably         has the characteristic that, on exhalation, exhaled gas is kept         separate from inhaled gas and on inhalation, when {dot over         (V)}E is greater than the flow of a first gas set (FGS) into the         circuit, the subject inhales FGS gas first and then inhales a         second gas set (SGS) gas, preferably said SGS containing CO₂ and         where SGS may be mostly previously exhaled gas. Any SGDB circuit         can be used to greater or lesser benefit, according to its         characteristics. We provide below detailed descriptions of         several alternate configurations and outline their particular         advantages and drawbacks with respect to measuring {dot over         (Q)} and related parameters outlined above.     -   2) a gas sample line (204.1) leading to a gas analyzer (204)         that monitors the concentration of gases, for example CO₂, O₂,         at the patient-circuit interface and outputs preferably an         electric signal corresponding to the concentrations (204.2) (for         example if the gases of interest are O₂ and CO₂, the “#17500 O₂         and CO₂ analyzer set” (Vacumed, Ventura Calif., USA))     -   3) a precise gas flow controller (200), preferably one that can         control the flow of one or more pressurized gases (such as         oxygen, air, CO₂) singly or in combination, and that can be set         manually or via an automated system such as via machine         intelligence (for example, the Voltek gas flow controller by         Voltek Enterprises, Toronto, Canada);     -   4) a source of FGS (201), preferably containing O₂ and /or air         with or without CO₂;     -   5) means (205) to identify phase of breathing, for example using         electronic pressure sensors with tubing to sample pressures at         the patient-circuit interface (205.1) or in other locations in         the circuit and generating electrical signal corresponding to         the sensed pressures. Such means will provide electrical signal         (205.2). Phase of breathing can also be determined from analysis         of gas sensor output by machine intelligence.     -   6) a computer or machine intelligence (207) which records,         stores, analyzes signals from gas analyzer (204) and pressure         transducer (if present), contains a predetermined set of         instructions regarding the analysis of data such as calculation         of {dot over (Q)} and physiologic parameters, determination of         phase of respiration, display of information on a computer         screen, and control of gas flow controller (200) including the         timing, sequence and flow of gas.     -   7) wherein said device may be utilized for non-invasive         measurement and determination of {dot over (Q)} and other         parameters such as {dot over (V)}A, {dot over (V)}CO₂, P         vCO₂-oxy, true P vCO₂, PaCO₂, pulmonary shunt, and anatomical         dead space         Detailed Description of Breathing Circuits

FIG. 5 shows a breathing circuit which provides sequential delivery of the FGS followed by the SGS when {dot over (V)}E exceeds FGSF, with the manifold containing the valves and the FGS reservoir bag and the expiratory gas reservoir bag remote from the patient. This improvement reduces the bulk of the patient manifold, and eliminates the possibility of the SGS mixing with the FGS due to vigorous exhalation.

Referring to FIG. 5, Patient (38) breathes via a Y connector (40). Valve (31) is an inspiratory valve and valve (33) is an expiratory valve. Valve (35) is a bypass valve in the bypass limb (34) that bypasses the expiratory valve (33) and has an opening pressure greater than inspiratory valve (31). Valves (35, 33) may be dose to or distal from the patient manifold as desired, as long as they are on the expiratory limb (39). However, in the preferred embodiment, they are distal to the patient to reduce the bulk of the patient manifold. Inspiratory valve (31) may be close to, or distal from, the patient manifold as desired, as long as it is on the inspiratory limb (32). In the preferred embodiment, it is distal to the patient as well. FGS enters the circuit via port (30).

Function:

During exhalation, increased pressure in the circuit closes inspiratory valve (31) and bypass valve (35). Gas is directed into the exhalation limb (39), past one-way valve (33) into the expiratory gas reservoir bag (36). Excess gas is vented via port (41) in expiratory gas reservoir bag (36). FGS enters via port (30) and fills FGS reservoir (37). During inhalation, inhalation valve (31) opens and FGS from the FGS reservoir (37) and FGS port (30) enter the inspiratory limb (32) and are delivered to the patient. If FGSF is less than {dot over (V)}E, the FGS reservoir (37) empties before the end of the breath, and continued respiratory effort results in a further reduction in pressure in the circuit. When the opening pressure of the bypass valve (35) is reached, it opens and gas from the expiratory gas reservoir (36) passes into the expiratory limb (39) and makes up the balance of the breath with SGS.

Thus when FGSF is less than {dot over (V)}E, the subject inhales FGS, then SGS, and no containation of FGS occurs.

FIG. 3B shows an alternate embodiment of the circuit illustrated in FIG. 5 where the passive expiratory valve (33) and expiratory bypass limb (34), and expiratory limb bypass valve (35) are replaced with a control valve that is triggered by the collapse of the inspiratory reservoir. Referring to FIG. 3B, a control valve (401) is placed in the expiratory limb (16) anywhere along its length between the patient port (10) and the expiratory reservoir bag (18). When the patient's V_(E) exceeds the FGSF during inspiration the reservoir bag (20) collapses. This is detected by pressure sensing means (405) through port (406) as an acute reduction in pressure. Pressure sensing means (405) could be an electronic pressure transducer capable of detecting changes 2 cm H₂O pressure, for example. Immediately afterwards, valve (401) is then opened by control means (403), which could be an electronic signal for activating a solenoid valve, for example, leading to depressurization and collapse of a balloon valve, as is known to those skilled in the art, resulting in SGS is being inhaled for the balance of inhalation. During exhalation, patient exhales through expiratory tube (16) past valve (401) into the SGS reservoir (18). At end of exhalation, as detected by pressure sensing means (405) as a reduction of pressure, valve (401) is dosed by control means (403), which could be an electronic signal for toggling a solenoid valve, for example, leading to pressurization and inflation of a balloon valve, as is known to those skilled in the art.

While the circuits of FIG. 5 and FIG. 3B present the advantages over the Fisher circuit of reducing the bulk of the patient manifold, and eliminating the possibility of the SGS mixing with the FGS due to vigorous exhalation, they still have the following drawback: When FGS reservoir (20, 37) is emptied and the patient is breathing SGS for the balance of an inspiration, the circuit does not deliver SGS alone but a mixture of SGS and FGS. The FGS continues to flow into the circuit and is drawn by inhalation past one-way inspiratory valve (31,3) and allows FGS gas to be inhaled from the inspiratory limb (32,14). To optimize the generation of data required to measure of cardiac output, it is necessary to redirect the FGS into the FGS reservoir (37,20) for the balance of inhalation after the initial collapse of the FGS reservoir. This would prevent mixing of FGS with SGS during the period of inhalation where the patient breathes SGS. This limitation of circuits illustrated in FIGS. 5 and 3B with respect to measuring cardiac output are shared with the Fisher circuit.

FIG. 3D shows an improved circuit that prevents contaition of the SGS by FGS when SGS is being delivered to the patient. Referring to FIG. 3D, FGS control valve (400) is added to the inspiratory limb (14) at some point between the FGS port (12) and the inspiratory valve (11). Pop-off valve (425) is connected to the inspiratory limb on the side of the FGS control valve (400) that is proximal to the inspiratory reservoir bag (425). During exhalation, gas passes from the patient port (10), through the expiratory one-way check valve (15) down the expiratory limb (16) into the expiratory reservoir bag (18). Excess gas exits the expiratory reservoir bag (18) at the opening (19) remote from the entrance. FGS enters the circuit at a constant flow via a fresh gas port (12). As the inspiratory one-way check valve (11) is dosed during exhalation, the fresh gas accumulates in the fresh gas reservoir bag (20). During inhalation, FGS entering from the port (12) and the FGS reservoir (20) passes through the inspiratory valve (11) and enters the patient. If the FGSF is less than {dot over (V)}E, the FGS reservoir bag (20) collapses, as detected by pressure sensing means (405) connected to pressure sensing port (406). FGS control valve (400) is closed via valve control means (403), and valve (17) in the bypass limb (13) opens, directing previously exhaled gas to the patient When the FGS control valve (400) is dosed, any FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (20) and not to the patient, who is receiving SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration to just before the next inspiration. FGS control valve (400) may be any type of valve, and is preferably an active valve such as a balloon valve, known to those skilled in the art, that can be controlled by automated means. The pop-off valve (425) opens when the reservoir bag (20) is full to prevent the reservoir bag (20) from overfilling.

The circuit illustrated in FIG. 5A is similar to that in FIG. 5 but has the addition of a FGS control valve (400), together with pressure sensing means (405) and port (406), and valve control means (403), added to the inspiratory limb of the circuit (32) distal to the one-way inspiratory valve (31) and proximal to the FGS inflow port (30). Similarly, a FGS control valve, together with pressure sensing means and port, and valve control means, may be added to the inspiratory limb (14) of the circuit illustrated in FIG. 3B positioned distal to the one-way inspiratory valve (31) and proximal to the FGS inflow port (12) to achieve the same result, namely, prevention of contamination of SGS by FGS when {dot over (V)}E exceeds FGSF and the FGSF reservoir bag is emptied.

We present two additional circuits that are configured by adding FGS control valve (400) together with pressure sensing means (405) and port (406), and valve control means (403), to the Fisher circuit and the circuit illustrated in FIG. 5 and removing the passive one way inspiratory valve (11, 31), as shown in FIGS. 3E and 5B respectively. These circuits function identically to those illustrated in FIGS. 3D and 5A with respect to complete separation of FGS and SGS during inhalation. In such a circuit, during inspiration, FGS control valve (400) is open until FGSF reservoir bag (20,37) is emptied, then it is closed so that any additional FGSF entering the circuit during the balance of inspiration is directed only to the reservoir bag (20) and not to the patient As the patient continues to inspire, bypass valve (17,35) opens allowing the patient to inhale SGS for the balance of inspiration.

Another embodiment of each of the circuits whereby the valves can be remote from the patient without loss of sequential delivery of FGS and SGS, such as those illustrated in FIGS. 5, 3B, 5A, 5B, 3C, 4B, is the replacement of separate inspiratory limbs and expiratory limbs with co-axially arranged inspiratory and expiratory limbs as shown in FIG. 6. FIG. 6A shows the preferred embodiment of the invention: The circuit valves are configured as in the circuit illustrated in FIG. 5A with the improvement of co-axially arranged inspiratory (59) and expiratory (51) limbs. The limbs (51, 59) are co-axial so that one limb is contained within the other for some length of tubing, with the limbs separating at some point along its length, such that the expiratory limb (51) leads to the exhaled gas reservoir (54) and the inspiratory limb (59) leads to the FGS reservoir (56). This has two important advantages over the circuit of FIG. 5:

-   -   1. A single tube is connected to the patient interface making it         easier to manage sick patients     -   2. The heat contained in the expiratory limb (51) warms the FGS         entering through the inspiratory limb (59).     -   3. If the inner tube is of a material that allows moisture to         pass through it but not gas, such as Nafion, will promote         moisture exchange as well, so that FGS will become slightly         moisturized and more comfortable for the patient to breathe if         the SGS is moist.

It should be understood that co-axial tubing may be used with any of the SGDB circuits described herein.

Description of a Preferred Embodiment

Referring to FIG. 6A, Patient port (50) opens directly to the inspiratory limb (59) and expiratory limb (51) without a Y connector, where the limbs are arranged co-axially. Valve (31) is an inspiratory valve and valve (33) is an expiratory valve. Valve (35) is a bypass valve in the bypass limb (34) that bypasses the expiratory valve (33) and has an opening pressure greater thin inspiratory valve (31). Valves (35, 33) are preferably distal from the patient on the expiratory limb (51) to reduce the bulk of the patient interface. Inspiratory valve (31) is also preferably distal from, the patient on the inspiratory limb (59). FGS enters the circuit via port (30). FGS control valve (400) is on the inspiratory limb (59) between port (30) and inspiratory valve (31). FGS reservoir bag (37) is connected to inspiratory limb (59) distal to the patient, past port (37). SGS reservoir bag (36) is distal to the patient on the expiratory limb (51) past expiratory valve (33) and bypass valve (35). Excess expiratory gas vents to the atmosphere via port (41). Pressure sensing means (405) is connected to pressure sensing port (406) which is connected to the patient port (50), and valve control means (403). Pressure sensing port (406) may be connected to the co-axial inspiratory (59) and expiratory limb arrangement (51) anywhere along its length between the inspiratory valve (31) and the patient port (50) or between the expiratory valve (33) and the patient Pop-off valve (425) is connected to the inspiratory limb on the side of the FGS control valve (400) that is proximal to the inspiratory reservoir bag (425).

Function:

During exhalation, increased pressure in the circuit closes inspiratory valve (31) and bypass valve (35). Gas is directed into the exhalation limb (51), past one-way valve (33) into the expiratory gas reservoir bag (36). Excess gas is vented via port (41) in expiratory gas reservoir bag (36). FGS enters via port (30) and fills FGS reservoir (37). During inhalation, inhalation valve (31) opens and FGS from the FGS reservoir (37) and FGS port (30) enter the inspiratory limb (59) and are delivered to the patient If FGSF is less than {dot over (V)}E, the FGS reservoir (37) empties before the end of the breath, and continued respiratory effort results in a further reduction in pressure in the circuit. When the opening pressure of the bypass valve (35) is reached, it opens and gas from the expiratory gas reservoir (36) passes into the expiratory limb (39) and makes up the balance of the breath with SGS. The emptying of FGS reservoir bag (37) is detected by pressure sensing means (405) such as an electronic pressure transducer, known to those skilled in the art, connected to pressure sensing port (406), and FGS control valve (400) such as a balloon valve known to those skilled in the art, is closed via valve control means (403) such as access to gas pressure controlled by an electronically toggled solenoid valve known to those skilled in the art When the FGS control valve (400) is closed, any additional FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (20) and not to the patient, who is inhaling only SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration, as sensed by the reverse of pressure by the pressure sensing means (405), to just before the next inspiration, also sensed by pressure changes in the breathing circuit. Pop-off valve (425) prevents the FGS reservoir bag (20) from overfilling when FGS exceeds {dot over (V)}E.

Thus when FGSF is less than {dot over (V)}E, the subject inhales FGS, then SGS, and no contamination of SGS with FGS occurs.

Use of Circuits for Ventilated Patients

Any of the SGDB circuits disclosed herein as well as the Fisher circuit can be used for a patient under controlled ventilation by enclosing the FGS reservoir (20) and exhaled gas reservoir (18) within a rigid container (21) with exit ports for the inspiratory limb of the circuit (24) and expiratory limb of the circuit (25) and port for attachment to a patient interface of a ventilator (22) as illustrated in FIG. 4. In FIG. 4, the inspiratory limb (500) represents the inspiratory limb of any of the SGDB circuits herein described, and expiratory limb (501) corresponds to the expiratory limb of any of the SGDB circuits herein described. The FGS reservoir bag (20) and expiratory gas reservoir bag (18) are enclosed in a rigid air-tight container such that the inspiratory limb (500) enters the container via port (24) and expiratory limb (501) enters the container via port (25) such that the junctions of the outside of the limbs form an air-tight seal with the inside surface of the ports. A further port (22) is provided for attachment of the Y piece of any ventilator (23). Detachment from the ventilator allows the circuit to be used with a spontaneously breathing patient. During the inspiratory phase of the ventilator, the pressure inside the container (21) rises putting the contents of the FGS reservoir bag (20) and the expiratory gas reservoir bag (18) under the same pressure. Since the opening pressure of the inspiratory valve is less than that of the bypass valve for circuits using passive bypass valves (for example those shown in FIGS. 2, 3, 5, 5B, 5A, 3E, and 3D), the FGS reservoir (20) will be emptied preferentially. When the FGS reservoir (20) is empty, the pressure in the container (21) and inside the expiratory gas reservoir (18) will open the bypass valve (35, 17, 206) and begin emptying exhaled gas reservoir (18) delivering SGS to the patient For circuits using an actively engaged control valve (400) in the inspiratory limb of the circuit, a valve opening detection means (407) such as an electronic circuit that is broken by the opening of the valve when the valve is part of a closed electronic circuit, not shown, detects opening of the one way valve (35, 17, 206) in the exhalation bypass limb. The FGS control valve (400) is then closed, directing FGS into the FGS reservoir bag until the collapse of the FGS reservoir during the next inspiratory phase.

During the exhalation phase of the ventilator, the ventilator's expiratory valve is opened and contents of the container (21) are opened to atmospheric pressure, allowing the patient to exhale into the expiratory gas reservoir (18) and the FGS to flow into the FGS reservoir bag (20). Thus, the FGS and SGS are inhaled sequentially during inhalation with controlled ventilation without mixing of FGS with SGS at any time.

FIG. 4B shows the ventilator configuration described above as used with the preferred circuit shown in FIG. 6A. This is the preferred embodiment for ventilated patients.

The primary difference between the standard anesthetic circle circuit of the prior art (FIG. 12) and the circuits disclosed herein is that with the circuits disclosed herein, both a SGS reservoir (18) and a FGS reservoir (20) are in the rigid box. With the valve configurations disclosed herein, there will be sequential delivery of the FGS, then the SGS, when {dot over (V)}E exceeds the FGSF. This does not occur with the standard anesthetic circle circuit, even if the CO₂ absorber is removed from the circuit.

CIRCUIT FOR CALCULATION OF {dot over (Q)} AND RELATED PHYSIOLOGIC PARAMETERS WHILE MODIFYING SECOND GAS SET

FIG. 7 shows the preferred circuit for measuring cardiac output while maintaining the ability to modify the SGS. The circuit consists of the following components:

200 patient port

201 three-port connector

202 expiratory limb

203 expiratory valve

204 canister on bypass conduit that may be switched to be empty, contain CO₂ absorbing crystals, zeolyte, charcoal or similar substance that filters anesthetic agents, or hopcalite for filtering carbon monoxide

205 bypass conduit

206 one-way bypass valve with opening pressure slightly greater than that of the inspiratory valve (219)

207 SGS reservoir bag

208 port in rigid container for entrance of expiratory limb of circuit in an air-tight manner

209 exit port for expired gas from expired gas reservoir

210 a 2-way manual valve that can be turned so that the gas in the rigid box (216) is continuous with either the ventilator Y piece (211) or the manual ventilation assembly consisting of ventilating bag (212) and APL valve (213)

211 the ventilator Y piece

212 the ventilation bag

213 APL valve

214 ventilation port in rigid box (216)

215 FGS reservoir

216 rigid box

217 port in rigid container for entrance of inspiratory limb of circuit (220) in an air-tight manner

218 FGS inlet port

219 inspiratory valve

220 inspiratory limb

221 bypass limb proximal to canister (204)

400 active FGS Control valve

403 valve control means

407 bypass valve opening sensing means

Function of the Circuit as an Anesthetic Circuit:

For spontaneous ventilation, 3-way valve (210) is open between rigid container (216) and manual ventilation assembly consisting of ventilation bag (212) and APL valve (213). When the patient exhales, increased pressure in the circuit closes inspiratory valve (219) and bypass valve (206). Exhaled gas is directed into the exhalation limb (202), past one-way valve (203) into the expiratory reservoir bag (207). FGS enters via port (218) and fills the FGS reservoir (215). During inhalation, inhalation valve (219) opens and FGS from the FGS reservoir (215) and FGS port (218) enter the inspiratory limb (220) and are delivered to patient If FGSF is less than {dot over (V)}E, the FGS reservoir (215) empties before the end of the breath; continued respiratory effort results in a further reduction in pressure in the circuit. When the opening pressure of the bypass valve (206) is exceeded, it opens and gas from the expiratory gas reservoir (207) passes through the canister (204) into the rebreathing limb (221) and makes up the balance of the breath with SGS. The opening of bypass valve (206) is detected by valve opening sensing means (407) signals are sent to close FGS control valve (400) by activating valve control means (403). When the FGS control valve (400) is closed, any additional FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (215) and not to the patient When valve (400) is closed patient receives only SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration to just before the next inspiration. Phase of ventilation is sensed by sensor (407).

For the purposes of functioning as an anesthetic delivery circuit, part of the FGS entering the circuit would be the anesthetic vapor, for example Desflurane, and the canister (204) would contain CO₂ absorbent material. The SGS passes through the canister (204) but still contains expired O₂ and anesthetic, which can both be safely rebreathed by the patient In this respect, the circuit in FIG. 7 functions like a circle anesthetic circuit in which the FGSF containing O₂ and anesthetic can be reduced to match the consumption or absorption by the patient. However, by bypassing the canister (204), the circuit can be used for measuring cardiac output.

If the canister (204) is filled with hopcalite it can be used to remove carbon monoxide from the patient, since the SGS still contains expired O₂ and CO₂. If the canister (204) is filled with zeolite it can be used to remove volatile agents such as anesthetics from the patient.

Advantages of Circuit Over Previous Art

-   -   1. It is comparable to the circle anesthesia circuit with         respect to efficiency of delivery of anesthesia, and ability to         conduct anesthesia with spontaneous ventilation as well as         controlled ventilation.     -   2) It is often important to measure tidal volume and {dot over         (V)}E during anesthesia. With a circle circuit, a pneumotach         with attached tubing and cables must be placed at the patient         interface, increasing the dead-space, bulk and clutter at the         head of the patient. With our circuit, the pneumotach (or a         spirometer if the patient is breathing spontaneously) can be         placed at port (214) and thus remote from the patient.     -   3) Sasano (Anesth Analg 2001; 93:1188-1191) taught a circuit         that can be used to accelerate the elimination of anesthesia.         However that circuit required additional devices such as an         external source of gas (reserve gas), a demand regulator,         self-inflating bag or other manual ventilating device, 3-way         stopcock and additional tubing. Furthermore, Sasano did not         disclose a method whereby mechanical ventilation can be used. In         fact it appears that it cannot be used—patients must be         ventilated by hand for that method. With the apparatus and         method disclosed herein, there is no requirement for an         additional external source of gas or demand regulator;     -   4) the patient can be ventilated with the ventilation bag (212)         already on the circuit or the circuit ventilator, or any         ventilator; no other tubing or devices are required.     -   5) Circle circuits cannot deliver FGS and then SGS sequentially.         Such control is required to make physiological measurements such         as cardiac output during anesthesia.

With the circuit of FIG. 7, if the canister (204) is bypassed, the circuit becomes the equivalent of the one described in FIG. 5 with the addition of the ventilator apparatus shown in FIG. 4. With the circuit of FIG. 7, box (216) could be opened to atmosphere instead of connected to a ventilator, and the circuit could be used with spontaneously breathing patients for measuring cardiac output while modifying SGS.

It should be recognized to those skilled in the art that various embodiments of the invention disclosed in this patent application are possible without departing from the scope including, but not limited to:

-   -   a) using multiple inspiratory and expiratory limbs in         combination provided that:         -   i) the inspiratory and expiratory limbs are kept separate             except at a single point prior to reaching the patient where             they are joined         -   ii) each limb has the corresponding valves as in the             arrangement above, and         -   iii) the valves have the same relative pressures so as to             keep the inspired gas delivery sequential as discussed             above.     -   b) using active valves, for example electronic, solenoid, or         balloon valves, instead of passive valves, provided said valves         are capable of occluding the limbs, and means is provided for         triggering and controlling said active valves. The advantage of         active valves is more precise control. The disadvantage is that         they are more costly.     -   c) replacing reservoir bags with extended tubes or other means         for holding gases     -   d) surrounding valves in exhalation limb and/or in the         inspiratory limb of circuit with the exhaled gas reservoir         causing them to be surrounded by warm exhaled air and prevent         freezing and sticking of valves in cold environments.     -   e) Changing the composition of FGS and SGS to change alveolar         concentrations of gases other than CO₂, for example O₂. By         analogy to CO₂, with respect to O₂: alveolar PO₂ is determined         by FGS flow and the PO₂ of FGS. When PO₂ of SGS is the same as         the PO₂ in the alveoli, inhaling SGS does not change flux of O₂         in the alveoli. Therefore, those skilled in the art can arrange         the partial pressure of component gases in FGS and SGS and the         flows of FGS such that they can achieve any alveolar         concentration of component gases independent of {dot over (V)}E,         as long as {dot over (V)}E exceeds sufficiently flow of FGS.

As many changes can be made to the various embodiments of the invention without departing from the scope thereof; it is intended that all matter contained herein be interpreted as illustrative of the invention but not in a limiting sense.

To clarify the function of the automated cardiac output device, we will contrast it to a standard anaesthetic machine which has the same configureation of listed components.

-   -   1) The preferred SGDB circuits we describe differ from any         anaesthetic circuit The SGDB circuit first provides the FGS,         then the SGS. This allows the circuit to compensate for changes         in CO₂ elimination on any particular breath. For example, during         a small breath, the unused FGS remains in the FGS reservoir and         is available to provide the exact additional {dot over (V)}A for         each gas in the set when a larger breath is taken or frequency         of breathing increases subsequently. As a result, changes in         {dot over (V)}CO₂ can be instituted independent of breathing         pattern.     -   2) Anesthetic machines do not automatically alter the fresh gas         flows. Fresh gas flows are manually controlled by the         anesthesiologist     -   3) Anesthetic machines do not calculate {dot over (V)}A and         cannot calculate {dot over (V)}CO₂, and {dot over (Q)}.     -   4) Anesthetic machines cannot generate the data required to make         the calculations for {dot over (Q)} and its associated         parameters because the circuit is inappropriate and the gas         flows are not configured to be controlled by a computer.     -   5) The flowmeters on commonly used anesthetic machines are too         imprecise and inaccurate to perform these tests and         calculations. There is no need for such precision and accuracy         of flow for routine clinical anesthetic care.

9.0 Method of Generating Data Required to Make Calculations of {dot over (Q)} and Related Physiologic Parameters (See FIG. 11):

Cardiac Output can be measured in several ways according to the methods and apparatus disclosed herein. These include:

9.1 Set-Up Phase

-   -   9.1.1 Set Flow of FGS>{dot over (V)}E     -   9.1.2 Access default values     -   9.1.3 Check pressure sensor or PCO₂ sensor during inhalation. If         fresh gas reservoir collapsed or CO₂ is detected during         inhalation, increase FGS flow until the reservoir until         reservoir does not collapse fully and no CO₂ is detected during         inhalation     -   9.1.4 Identify PETCO₂ from the CO₂ gas analyzer

9.2 Find {dot over (V)}A via one of two methods:

-   -   9.2.1 Calculate {dot over (V)}A by inducing two reductions in         FGS flow below {dot over (V)}A without first identifying {dot         over (V)}A by following the following steps:         -   9.2.1.1 Calculate a preliminary minimum {dot over (V)}A for             the subject based on body weight, temperature, sex and other             parameters known to those skilled in the art.         -   9.2.1.2 Provide luxuriant FGS flow greater than the             patient's resting {dot over (V)}E until steady state             P_(ET)CO₂ is reached         -   9.2.1.3 Impose a {dot over (V)}A by setting FGS Flow below             assumed {dot over (V)}A, to VA_(x) preferably just below the             calculated preliminary {dot over (V)}A, for a time less than             or equal to a recirculation time, and measure P_(ET)CO₂ _(x)             , the end tidal CO₂ concentration during equilibrium if an             equilibrium end tidal value is reached within a             recirculation time, otherwise it is the equilibrium value of             end tidal CO₂ as extrapolated from the exponential rise in             end tidal CO₂ values within the recirculation time.         -   9.2.1.4 Set FGS flow above {dot over (V)}_(E) until steady             state P_(ET)CO₂ is reached as identified by a less than a             threshold change in PETCO₂ over a designated time period.             The actual thresholds and time periods are user defined             according to the circumstances of the test and can be             determined by those skilled in the art         -   9.2.1.5 Impose a {dot over (V)}A by setting FGS Flow below             assumed {dot over (V)}A, to {dot over (V)}A_(y) where {dot             over (V)}A_(y) is less than calculated preliminary minimum             {dot over (V)}A and not equal to {dot over (V)}A_(x), for a             time approximately equal to a recirculation time, about 30 s             at rest. Measure P_(ET)CO₂ _(y) , the end tidal CO₂             concentration during equilibrium if an equilibrium end tidal             value is reached within a recirculation time, otherwise it             is the equilibrium value of end tidal CO₂ as extrapolated             from the exponential rise in end tidal CO₂ values within the             recirculation time.         -   9.2.1.6 On a graph of P_(ET)CO₂ vs FGS flow, plot the points             (P_(ET)CO₂ _(y) , {dot over (V)}A_(y)) and (P_(ET)CO₂ _(x) ,             {dot over (V)}A_(x)). Extrapolate the line formed by             connecting these two point to intersect a horizontal line at             P_(ET)CO₂-resting P_(ET)CO₂. The FGS flow at the             intersection point is determined to be {dot over (V)}A.     -   9.2.2 Progressive Reduction of FGS flow method of finding {dot         over (V)}A:         -   9.2.2.1 Use FGS that preferably has no CO₂.         -   9.2.2.2 Wait for steady state as indicated by less than a             threshold change in PETCO₂ over a designated time period.             The actual thresholds and time periods are user defined             according to the circumstances of the test and can be             determined by those skilled in the art.         -   9.2.2.3 When in steady state, reduce FGS flow by a small             fixed flow, for example 0.1 L/min, preferably at regular             intervals of time or after each breath. Alternate flow             reduction rates could be used, and the reduction need not be             linear in time.         -   9.2.2.4 When P_(ET)CO₂ begins to rise above a threshold             value which is approximately the mean steady state             P_(ET)CO₂, continue the reduction in the FGS flow for a time             approximately equal to one recirculation time.         -   9.2.2.5 After approximately one recirculation time, usually             about 30 s, raise FGS flow above resting {dot over (V)}E. A             relation of P_(ET)CO₂ vs FGS flow is calculated and two             lines of best fit are calculated, one for the set of steady             state P_(ET)CO₂ values, and one for the set of raised             P_(ET)CO₂ values above the mean of the steady state values.             The FGS flow corresponding to the intersection of said lines             corresponds to {dot over (V)}A. FIG. 13 illustrates that             progressive reduction of SGF (labelled “FGF” in the figure)             results in a distinct inflection point when either PETCO₂ or             PETO₂ is graphed as a function of SGF. We define the SGF             corresponding to this inflection point as equal to {dot over             (V)}A.         -   9.2.2.6 These two methods of finding {dot over (V)}A are             physiologically equivalent and one may have some advantages             over the other in particular clinical or research             circumstances. The Progressive Reduction method should be             contrasted with the method for calculating {dot over (V)}A             taught by Preiss et al. (Canadian Patent Application             2346517). In that method, while fresh gas flow into a             sequential gas delivery circuit was reduced stepwise, after             each reduction, the subject was observed for several breaths             looking for an exponential rise in P_(ET)CO₂. The Preiss             method requires continued breathing at each fresh gas flow             looking for development of a new steady when fresh gas flow             falls below {dot over (V)}A. This process is very time             consuming and is unlikely to be tolerated by most patients.             If, in the attempt to shorten the time for finding the fresh             gas flow below {dot over (V)}A the fresh gas flow reduction             are large, resolution of critical fresh gas flow is lost. If             the steps are small, when the fresh gas flow is just barely             less than {dot over (V)}A, it will be difficult to discern             the small rise in PETCO₂ from the normal variation in             PETCO₂. The progressive breath-by-breath reduction in FGS             flow disclosed herein results in a rapid linear rise in             PETCO₂ and fall in PETCO₂ both of which can be used to             identify the FGS flow corresponding to {dot over (V)}A as             illustrated in FIG. 13.

9.3 Calculations with the Differential Fick Equation

There are two methods of calculating cardiac output with the Differential Fick equation. (It is understood that the general methods are disclosed without the details well known to those skilled in the art of the multiple standard corrections for temperature, moisture, barometric pressure and the like.):

-   -   9.3.1 Find {dot over (V)}A by the Progressive Reduction of FGS         flow method of finding {dot over (V)}A:         -   9.3.1.1 Find {dot over (V)}A         -   9.3.1.2 Set FGS Flow={dot over (V)}A and calculate {dot over             (V)}CO₂ using the equation {dot over (V)}CO₂={dot over             (V)}AF_(ET)CO₂.         -   9.3.1.3 Impose a transient step change in {dot over (V)}A to             {dot over (V)}A′ for a time approximately equal to a             recirculation time, about 30 s at rest, by changing FGS flow             to a value below {dot over (V)}A. To fully automate the             process, select a {dot over (V)}A′ that will be below the             {dot over (V)}A. Calculate {dot over (V)}CO₂′={dot over             (V)}A′×F_(ET)CO₂′. Where F_(ET)CO₂′ is the fractional end             tidal CO₂ concentration during equilibrium if an equilibrium             end tidal value is reached within a recirculation time,             otherwise it is the equilibrium value of end tidal CO₂ as             extrapolated from the exponential rise in end tidal CO₂             values within the recirculation time.         -   9.3.1.4 Calculate {dot over (Q)} according to the             differential Fick equation using {dot over (V)}CO₂, {dot             over (V)}CO₂′, and CCO₂ and CCO₂′ where CCO₂ and CCO₂′ are             the contents of CO₂ of end capillary blood as calculated             from P_(ET)CO₂, and P_(ET)CO₂′ using known relationships             between PETCO₂, and other characteristics related to the             blood such as hemoglobin concentration, temperature oxygen             partial pressure and other parameters that are accessible or             can be used as default values by those skilled in the art.         -   9.3.1.5 Calculate {dot over (Q)} according to the             differential Fick equation using {dot over (V)}CO₂ and             P_(ET)CO₂ data from steady state phase and step change phase             and the PaCO₂ from the Kim Rahn Farhi method. This allows             the identification of the PETCO₂-PaCO2 gradient without an             arterial blood sample.     -   9.3.2 Generate required data by inducing two reductions in FGS         flow below {dot over (V)}A without first identifying {dot over         (V)}A by following the following steps:         -   9.3.2.1 Calculate a preliminary minimum {dot over (V)}A for             the subject based on body weight, temperature, sex and other             parameters known to those skilled in the art.         -   9.3.2.2 Provide luxuriant FGS flow greater than the             patient's resting {dot over (V)}E until steady state             P_(ET)CO₂ is reached         -   9.3.2.3 Impose a {dot over (V)}A and hence a {dot over             (V)}CO₂ by setting FGS Flow below preliminary calculated             {dot over (V)}A, to VA_(x) preferably just below the             preliminarily calculated {dot over (V)}A, for a time less             than or equal to a recirculation time, and calculate {dot             over (V)}CO₂ _(x) using the equation {dot over (V)}CO₂ _(x)             ={dot over (V)}A_(x)×F_(ET)CO₂ _(x) where F_(ET)CO₂ _(x) is             the fractional end tidal CO₂ concentration during             equilibrium if an equilibrium end tidal value is reached             within a recirculation time, otherwise it is the equilibrium             value of end tidal CO₂ as extrapolated from the exponential             rise in end tidal CO₂ values within the recirculation time.         -   9.3.2.4 Set FGS flow above V_(E) until steady state             P_(ET)CO₂ is reached as identified by a less than a             threshold change in PETCO₂ over a designated time period.             The actual thresholds and time periods are user defined             according to the circumstances of the test and can be             determined by those skilled in the art         -   9.3.2.5 Impose a transient step change in {dot over (V)}A to             {dot over (V)}A_(y) where {dot over (V)}A_(y) is less than             calculated {dot over (V)}A and not equal to {dot over             (V)}A_(x), for a time approximately equal to a recirculation             time, about 30 s at rest. Calculate {dot over (V)}CO₂             _(y)={dot over (V)}A_(y)×F_(ET)CO₂ _(y) . F_(ET)CO₂ _(y) is             the end tidal CO₂ concentration during equilibrium if an             equilibrium end tidal value is reached within a             recirculation time, otherwise it is the equilibrium value of             end tidal CO₂ as extrapolated from the exponential rise in             end tidal CO₂ values within the recirculation time.         -   9.3.2.6 Calculate {dot over (Q)} according to the             differential Fick equation using {dot over (V)}CO₂ _(x) ,             {dot over (V)}CO₂ _(y) , and and CCO₂ _(x) and CCO₂ _(y)             where CCO₂ _(x) and CCO₂ _(y) are the contents of CO₂ of end             capillary blood as calculated from P_(ET)CO₂ _(x) , and             P_(ET)CO₂ _(y) using known relationships between PERCO₂, and             other characteristics related to the blood such as             hemoglobin concentration, temperature oxygen partial             pressure and other parameters that are accessible or can be             used as default values by those skilled in the art.         -   9.3.2.7 Calculate {dot over (Q)} according to the             differential Fick equation using {dot over (V)}CO₂ and             P_(ET)CO₂ data from steady state phase and step change phase             and the PaCO₂ from the Kim Rahn Farhi method to identify the             PETCO₂-PaCO2 gradient. This allows the identification of the             PETCO₂-PaCO₂ gradient without an arterial blood sample.

Difference between this method and previous methods to perform the differential Fick:

-   -   (a) With the new method, the decrease in {dot over (V)}CO₂ is         performed by reducing the FGF to a SGDB circuit as opposed to         insertion of a deadspace at the patient-circuit interface. As a         result, if the subject increases his breathing rate or breath         size, there is no change in {dot over (V)}CO₂ and the         calculations via the differential Fick equation are not         affected.     -   (b) The {dot over (V)}CO₂ is known using the {dot over (V)}A         (identified by one of the new or the previously disclosed         method) and the PETCO₂, two robust and highly reliable measures.         This is unlike the need for a pneumotachymeter and the         error-prone breath-by-breath analysis of {dot over (V)}CO₂         required by previous art.     -   (c) {dot over (V)}A is not identified with the previous         differential Fick methods.     -   (d) The PETCO₂ to PaCO₂ gradient is calculated from two         independently derived values in the same subject. In the         previous art, this gradient is calculated from empirical         formulae derived from averaged values and do not necessarily         apply to the subject.

Therefore our method provides more accurate values for {dot over (V)}CO₂, {dot over (V)}CO₂′ and PaCO₂ than the previous art.

9.4 Kim-Rahn-Farhi

-   -   9.4.1 A period of reduced FGS flow simulates complete or partial         breath holding. The PETCO₂ of each breath is equivalent to a         sequential alveolar sample in the KRF prolonged exhalation         method. The substitution of sequential PETCO₂ values for         sequential samples from a single exhalation is used to calculate         true P vCO₂, P vCO₂-oxy, PaCO₂ and hemoglobin O₂ saturation in         mixed venous blood S vO₂ using the Kim Rahn Farhi method.     -   9.4.2 {dot over (Q)} can be calculated using the Fick approach         where the P vCO₂-oxy and PaCO₂ as calculated by the Kim Rahn         Farhi method are used to calculate the respective CO₂ contents         using methods well known to those skilled in the art, and the         {dot over (V)}CO₂ is as calculated from {dot over (V)}A and         FETCO₂ as derived in the sequence of steps described above.     -   9.4.3 Mxed venous O₂ hemoglobin saturation are calculated as         follows. {dot over (V)}O₂ is calculated from {dot over         (V)}O₂={dot over (V)}A×(FIO₂−FETO₂ ) where FIO₂ and FETO₂ are         the fractional concentration of inspired and end tidal O₂         respectively. Using {dot over (V)}O₂, {dot over (Q)} as         calculated by Differential Fick or Kim Rahn Farhi or Fisher         Method, end capillary O₂ oxygen content (assuming end capillary         blood is fully saturated with oxygen), Mixed venous O₂         saturation can be calculated from the standard Pick equation.     -   9.4.4 Information regarding the arterial O₂ hemoglobin         saturation (SaO₂) (as read from a non-invasive commonly         available pulse oximeter that makes the measurement by shining         an infrared light through a finger), and the S vO₂ can be used         to calculate the fraction of shunted blood ({dot over (Q)}_(S))         (assuming fully oxygenated blood in the end pulmonary capillary)         by using the following equation         ${\overset{.}{Q}s} = \frac{{\left( {{Sp}O}_{2} \right)\overset{.}{Q}t} - {\left( {{Sa}O}_{2} \right)\overset{.}{Q}p}}{S\overset{\_}{v}O_{2}}$

Our method of performing the Kim Rahn Farhi is an improvement over the previous art in that

-   -   (a) Test is performed simultaneously with a test for         differential Fick in spontaneously breathing subject.     -   (b) Data are pooled with the test as outlined above so         calculation of {dot over (V)}CO₂, is simultaneous to the other         calculations. In the previous art, the {dot over (V)}CO₂,         calculation cannot be done during a breath hold or simulated         breath hold by rebreathing.     -   (c) {dot over (V)}CO₂, measurement does not require a         pneumotachymeter which is expensive, cumbersome and error-prone.         In the previous art, {dot over (V)}CO₂, required for the         calculation of {dot over (Q)} required additional apparatus such         as pneumatchymeter or gas collection and volume measuring         apparatus.

9.5 Fisher E-I Test

-   -   9.5.1 Calculate {dot over (V)}A from the calibration phase, set         FGS flow={dot over (V)}A.     -   9.5.2 With FGS Flow at {dot over (V)}A, the PCO₂ in the FGS is         changed to any value and held at that value for a time         approximately equal to a recirculation time, about 30 s at rest     -   9.5.3 P vCO₂-oxy is calculated using the PETCO₂-PICO₂ method         described by Fisher.     -   Our method of the Fisher E-I test is an improvement over the         previous art in that the effect of change in breath size on the         equilibrium value of PETCO₂ is minimized by the SGDB circuit         such that a larger breath delivers physiologically neutral         previously expired gas instead of additional test gas.

10.0 Method of finding {dot over (V)}E using progressive reduction of FGS Flow:

-   -   10.1 Use FGS that preferably has no CO₂     -   10.2 Wait for steady state as indicated by less than a threshold         change in PETCO₂ over a designated time period. The actual         thresholds and time periods are user defined according to the         circumstances of the test and can be determined by those skilled         in the art     -   10.3 When in steady state, reduce FGS flow by a small fixed         flow, for example 0.1 L/min, preferably at regular intervals of         time or after each breath. Alternate flow reduction rates could         be used, and the reduction need not be linear in time.     -   10.4 Using a means for measuring pressure within the FGS         reservoir in the breathing circuit, for example a pressure         transducer, monitor when the FGS reservoir bag first collapses.         {dot over (V)}E is the FGS flow rate when the reservoir bag         first collapses.

11.0 Method for Measuring Anatomical Dead Space

11.1 Measure {dot over (V)}E and {dot over (V)}A using any of the methods disclosed above

11.2 Measure the respiratory rate, preferrably using the apparatus for cardiac output disdosed herein.

11.3 Calculate Anatomical Dead Space {dot over (V)}DAN=({dot over (V)}E−{dot over (V)}A)/respiratory rate

As many changes can be made to the various embodiments of the invention without departing from the scope thereof; it is intended that all matter contained herein be interpreted as illustrative of the invention but not in a limiting sense.

REFERENCE LIST

-   (1) Ganz W, Donoso R, Marcus H S, Forrester J S, Swan H J. A new     technique for measurement of cardiac output by thermodilution in     man. Am J Cardiol 1971; 27(4):392-396. -   (2) Stetz C W, Miller R G, Kelly G E, Raffin T A. Reliability of the     thermodilution method in the determination of cardiac output in     clinical practice. Am Rev Respir Dis 1982; 126(6):1001-1004. -   (3) Critchley L A, Critchley J A. A meta-analysis of studies using     bias and precision statistics to compare cardiac output measurement     techniques. J Clin Monit Comput 1999; 15(2):85-91. -   (4) Imhoff M, Lehner J H, Lohlein D. Noninvasive whole-body     electrical bioimpedance cardiac output and invasive thermodilution     cardiac output in high-risk surgical patients. Crit Care Med 2000;     28(8):2812-2818. -   (5) Koobi T, Kauidnen S, Kauppinen P. Comparison of methods for     cardiac output measurement Crit Care Med 2001; 29(5)-1092. -   (6) Osterlund B, Gedeon A, Krill P, Johansson G, Reiz S. A new     method of using gas exchange measurements for the noninvasive     determination of cardiac output: clinical experiences in adults     following cardiac surgery. Acta Anaesthesiol Scand 1995;     39(6):727-732. -   (7) Richard R, Lonsdorfer-Wolf E, Charloux A, Doutreleau S, Buchheit     M, Oswald-Mammosser M et al. Non-invasive cardiac output evaluation     during a maximal progressive exercise test, using a new impedance     cardiograph device. Eur J Appl Physiol 2001; 85(34):202-207. -   (8) Nottin S, Vinet A, Lecoq A M, Guenon P, Obert P. [Study of the     reproducibility of cardiac output measurement during exercise in     pre-pubertal children by doppler echocardiography and CO2     inhalation]. Arch Mal Coeur Vaiss 2000; 93(11):1297-1303. -   (9) Sakka S G, Reinhart K, Wegscheider K, Meier-Hellmann A. Is the     placement of a pulmonary artery catheter still justified solely for     the measurement of cardiac output? J Cardiothorac Vasc Anesth 2000;     14(2):119-124. -   (10) Zollner C, Haller M, Weis M, Morstedt K, Lamm P, Kilger E et     al. Beat-to-beat measurement of cardiac output by intravascular     pulse contour analysis: a prospective criterion standard study in     patients after cardiac surgery. J Cardiothorac Vasc Anesth 2000;     14(2):125-129. -   (11) Nakonezny P A, Kowalewski R B, Ernst J M, Hawkley L C, Lozano D     L, Litvack D A et al. New ambulatory impedance cardiograph validated     against the Minnesota Impedance Cardiograph. Psychophysiology 2001;     38(3):465-473. -   (12) Jin X, Weil M H, Tang W, Povoas H, Pernat A, Xie J et al.     End-tidal carbon dioxide as a noninvasive indicator of cardiac index     during circulatory shock. Crit Care Med 2000; 28(7):2415-2419. -   (13) Preiss D A. A new method for measurement of carbon dioxide flux     in the lungs during breathing. Toronto: Graduate Department of     Chemical Engineering and applied Chemistry, University of Toronto,     2003. 

1. A breathing circuit for use with a first gas set (FGS) and a second gas set (SGS), said circuit comprising means for keeping separate the FGS and SGS, an FGS reservoir, and a means for sequentially delivering to a patient on inspiration, first the FGS, and, when FGS reservoir is emptied, subsequently delivers substantially SGS for the balance of inspiration.
 2. A breathing circuit for use with a first gas set (FGS) and a second gas set (SGS), said circuit comprising means for keeping separate the FGS and SGS, an FGS reservoir, and a means for sequentially delivering to a patient on inspiration, first the FGS, and, on inspiration, when FGS reservoir is emptied, subsequently delivers SGS for the balance of inspiration.
 3. The circuit of claim 1 or claim 2 comprising: a. an inspiratory limb with a port for entry of FGS, a FGS reservoir and FGS flow control means b. an expiratory limb containing an exit port for exhaled gas, SGS reservoir, and SGS flow control means for directing the flow towards the SGS reservoir during exhalation, and for directing the flow of SGS in the expiratory limb towards the patient during a portion of inspiration.
 4. The circuit of claim 3 where the FGS flow control means comprises at least one unidirectional valve that opens toward the patient.
 5. The circuit of claim 3 where the FGS flow control means comprises a FGS controlled valve activated by a FGS valve control means, which allows FGS to flow to the subject during inspiration until the FGS reservoir has been emptied and then prevents FGS from flowing to the subject until the next inspiration begins.
 6. The circuit of claim 5 where the FGS flow control means additionally comprises at least one uni-directional valve that opens toward the patient, located between the controlled valve and the patient.
 7. The circuits of claims 4, 5 or 6 wherein the SGS flow control means comprises an exhalation valve on the expiratory limb, and a bypass valve on a bypass limb connected to the expiratory limb, said bypass limb bypassing said exhalation valve, whereby said bypass valve is opened during inspiration only once the FGS reservoir has been emptied.
 8. The circuit of claims 4, 5 or 6 wherein the SGS control means comprises a SGS controlled valve activated by a SGS valve control means, said SGS valve control means which opens said SGS controlled valve to allow SGS to be inspired by the subject during inspiration once the inspiratory reservoir has been emptied and closes it after expiration.
 9. A breathing circuit comprising: a. an inspiratory limb with a port for entry of FGS, a FGS reservoir and FGS flow control means, whereby the FGS control means directs FGS into the FGS reservoir during the portion of inspiration after the FGS reservoir is emptied preventing FGS flow to the patient prior to the beginning of the next inspiration, b. an expiratory limb containing an exit port for exhaled gas, an SGS reservoir, and exhalation valve for directing the flow towards the SGS reservoir during exhalation, c. a bypass limb connecting the inspiratory and expiratory limbs, containing a bypass flow control means which directs flow of the SGS from the SGS reservoir to the patient through the inspiratory limb during the portion of inspiration from when the FGS reservoir is emptied until the end of inspiration.
 10. The circuit of claim 9 where the FGS flow control means comprises at least one unidirectional valve that opens toward the patient.
 11. The circuit of claim 9 where the FGS flow control means comprises a FGS controlled valve activated by a FGS valve control means, which allows FGS to flow to the subject during inspiration until the inspiratory reservoir has been emptied and then prevents FGS from flowing to the subject until the next inspiration begins.
 12. The circuit of claim 11 where the FGS flow control means additionally comprises at least one uni-directional valve that opens toward the patient, located between the controlled valve and the patient.
 13. The circuits of claims 10, 11, or 12 wherein the SGS flow control means comprises an exhalation valve on the expiratory limb, and a bypass valve on a bypass limb connected to the expiratory limb, said bypass limb bypassing said exhalation valve, whereby said bypass valve is opened during inspiration only once the FGS reservoir has been emptied.
 14. The circuit of claims 10, 11, or 12 wherein the SGS control means comprises a SGS controlled valve activated by a SGS valve control means, said SGS valve control means which opens said SGS controlled valve to allow SGS to be inspired by the subject during inspiration once the inspiratory reservoir has been emptied and closes it after expiration.
 15. The circuits of claims 1, 2 or 9 whereby the inspiratory and expiratory limbs are co-axial.
 16. The circuits of claim 15 whereby one of the limbs is comprised of a material that allows passage of moisture to the other but keeps the gases in the limbs separate
 17. The circuits of claim 1, 2 or 9 whereby the reservoirs are contained in a sealed container with openings for the inspiratory and expiratory limbs, and with opening for connection to a ventilator.
 18. The circuits of claim 1, 2 or 9 additionally comprising means for detecting when SGS is being delivered to the patient, with FGS control means using said detecting means to determine when to direct FGS to the FGS reservoir and prevent FGS from being delivered to the patient.
 19. The circuits of claims 1, 2 or 9 whereby the FGS consists of one or more gases in combination and in varying concentrations.
 20. The circuits of claims 1, 2 or 9 whereby the FGS consists of air.
 21. The circuits of claims 1, 2 or 9 whereby the FGS consists of O₂.
 22. The circuits of claims 1, 2 or 9 whereby the FGS consists of air and O₂ mixed.
 23. The circuits of claims 1, 2 or 9 whereby the FGS contains CO₂.
 24. The circuits of claim 1, 2 or 9 whereby the SGS consists of one or more gases in combination and in varying concentrations.
 25. The circuits of claim 1, 2 or 9 whereby the SGS comprises previously exhaled gas.
 26. The circuits of claim 1, 2 or 9 whereby the SGS comprises a mixture of previously exhaled gas and an exogenous set of gases.
 27. The circuits of claim 1, 2 or 9 further comprising means for altering the composition of SGS delivered to the patient.
 28. The circuits of claim 27 wherein said SGS altering means comprises CO₂ absorbing material.
 29. The circuits of claim 27 wherein said SGS altering means comprises Zeolite for elimination of anaesthetics or vapour anaesthetic agents.
 30. The circuits of claim 27 wherein said SGS altering means comprises Hopcalite for elimination of carbon monoxide.
 31. The circuits of claims 1, 2 or 9 whereby the portion of the inspiratory limbs and expiratory limbs that contain the valves or flow control means are contained within the SGS reservoir.
 32. The circuits of claims 1, 2 or 9 wherein said SGS reservoirs are bags or extended tubes sufficiently large to provide the functions of SGS.
 33. An apparatus to measure cardiac output ({dot over (Q)}) and other parameters such as alveolar ventilation ({dot over (V)}A), minute ventilation ({dot over (V)}_(E)), minute CO₂ elimination from the lung ({dot over (V)}CO₂), minute oxygen consumption ({dot over (V)}O₂), oxygenated mixed venous partial pressure of CO₂, (P vCO₂-oxy), true mixed venous partial pressure of CO₂ (P vCO₂), PaCO₂, mixed venous oxygen saturation (SvO₂), pulmonary shunt, and anatomical dead space, comprises: a) Any breathing circuit wherein when the subject's minute ventilation exceeds a first gas set (FGS) flow into the circuit, the balance of his/her ventilation is supplied from a second gas set (SGS). b) gas analyser means for monitoring gas concentrations of the patient's breath c) a gas flow control means for controlling the rate of FGS flow into the breathing circuit d) optionally wherein FGS is provided to the patient first followed by SGS.
 34. The apparatus of claim 33 further comprising a first gas set (FGS), and a second gas set (SGS), said second gas set which may comprise previously exhaled gases or exogenous gases or both.
 35. The apparatus of claim 33 further comprising means to identify phase of breathing.
 36. The apparatus of claim 33 further comprising machine intelligence capable of controlling the gas flow control means, receiving the output of the gas sensor means and means to identify phased of breathing, and performing the calculations for measuring cardiac output and other parameters.
 37. The apparatus of claim 33 wherein the breathing circuit is the circuit of claims 1, 2 or
 9. 38. The apparatus of claim 33 wherein the breathing circuit is that described by Fisher in U.S. Pat. No. 6,622,725.
 39. The apparatus of claim 33, 34, or 36 where said gas flow control means is capable of controlling and mixing the flows of several component gases to constitute FGS.
 40. The apparatus of claim 33, 34 or 36 where FGS comprises O₂.
 41. The apparatus of claim 33, 34 or 36 where FGS comprises air.
 42. The apparatus of claim 33, 34 or 36 where FGS comprises O₂ and air in any proportion.
 43. The apparatus of claim 40, 41, or 42 where FGS further comprises any proportion of CO₂, anesthetic or other gas or vapour.
 44. The method of using the apparatus of claims 33, 34 or 36 for determining {dot over (Q)}, {dot over (V)}A, {dot over (V)}_(E), {dot over (V)}CO₂, {dot over (V)}O₂, P vCO₂-oxy, true P vCO₂, PaCO₂, SvO₂, pulmonary shunt, and anatomical dead space.
 45. A method of identifying the alveolar ventilation ({dot over (V)}_(A)) using the apparatus of claim 33 comprising: a. setting the FGS flow into the circuit at a rate greater than the subject's minute ventilation {dot over (V)}_(E) b. measuring one or more end tidal CO₂ concentrations (P_(ET)CO₂ ) in a steady state c. progressively lowering the FGS flow into the circuit, either breath by breath or continuously while measuring PETCO₂ of the subject d. identifying a rise in P_(ET)CO₂ above a threshold e. determining {dot over (V)}_(A) as the rate of FGS flow into the circuit at the beginning of the rise in P_(ET)CO₂ above said threshold.
 46. The method of claim 45 wherein the beginning of the rise in P_(ET)CO₂ is determined by: a. after identifying the rise in PETCO₂ above said threshold, collecting one or more successive PETCO₂ values prior to a recirculation time b. fitting a straight line to said values of P_(ET)CO₂ on a graph of PETCO₂ vs FGS flow. c. determining the FGS flow at which the P_(ET)CO₂ of said line equals one of, or the average of several of, the P_(ET)CO₂ values at steady state, said FGS flow being equal to {dot over (V)}_(A).
 47. A method of measuring the alveolar ventilation ({dot over (V)}_(A)) using the apparatus of claim 33 comprising: a. estimating a preliminary minimum {dot over (V)}A for the subject based on body weight, temperature, and sex. b. Providing FGS flow greater than the patient's resting {dot over (V)}E until steady state P_(ET)CO₂ is reached c. Setting FGS flow below said estimated {dot over (V)}A, to a flow {dot over (V)}_(A) _(x) for a time less than or equal to a recirculation time, and measure P_(ET)CO₂ _(x) , the end tidal CO₂ concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise measuring P_(ET)CO₂ _(x) the equilibrium value of end tidal CO₂ as extrapolated from the exponential rise in end tidal CO₂ values within the recirculation time. d. Setting FGS flow above {dot over (V)}E until steady state P_(ET)CO₂ is reached. e. Setting FGS Flow below estimated {dot over (V)}A, to flow {dot over (V)}A_(y) where {dot over (V)}A_(y) is not equal to {dot over (V)}A_(x), for a time less than or equal to a recirculation time, and measuring P_(ET)CO₂ _(y) , the end tidal CO₂ concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise measuring P_(ET)CO₂ _(y) as the equilibrium value of end tidal CO₂ as extrapolated from the exponential rise in end tidal CO₂ values within the recirculation time. f. On a graph of P_(ET)CO₂ vs FGS flow, plot the points (P_(ET)CO₂ _(y) , {dot over (V)}A_(y)) and (P_(ET)CO₂ _(x) , {dot over (V)}A_(x)) extrapolate the line formed by connecting these two points to intersect a horizontal line at P_(ET)CO₂=resting P_(ET)CO₂. g. Determining {dot over (V)}A to be the FGS flow corresponding to the intersection point .
 48. The method of claims 45, 46, or c wherein the {dot over (V)}_(A) so determiined is utilized to determine the {dot over (V)}CO₂ as {dot over (V)}_(A)×F_(ET)CO₂ during the steady state.
 49. The method of claims 45, or 46, wherein O₂ is used instead of CO₂ and the PETO₂ level drops below a threshold value, instead of PETCO₂ rising above a threshold value.
 50. The method of claims c wherein PETO₂ values are measured instead of PETCO₂ values.
 51. A method for measuring {dot over (V)}CO₂ of a subject breathing on any breathing circuit wherein when the subject's minute ventilation exceeds a first gas set (FGS) flow into the circuit, the balance of his/her ventilation is supplied from a second gas set (SGS).comprising: a. Setting the FGS flow into the circuit at a rate equal to or above the subject's {dot over (V)}_(A) b. Measuring the average CO₂ concentration of gas exiting the circuit c. Determining said {dot over (V)}CO₂ to be the average CO₂ concentration×FGS flow rate
 52. A method for determining {dot over (V)}_(A) of a subject comprising measuring {dot over (V)}CO₂ using the method of claim 51, measuring the subjects FETCO₂ and determining {dot over (V)}_(A) as {dot over (V)}CO₂/FETCO₂.
 53. A method for measuring {dot over (V)}O₂ of a subject breathing on any breathing circuit wherein when the subject's minute ventilation exceeds a first gas set (FGS) flow into the circuit, the balance of his/her ventilation is supplied from a second gas set (SGS) comprising: a. Setting the FGS flow into the circuit at a rate equal to or above the subject's {dot over (V)}_(A) b. Measuring the average O₂ concentration of gas exiting the circuit c. Determining said {dot over (V)}O₂ to be the FGS flow rate×[average O₂ concentration of FGS−average O₂ concentration of gas exiting the circuit]
 54. The method of claim 51 wherein the circuit is a SGDB circuit.
 55. The method of claim 53 wherein the circuit is a SGDB circuit.
 56. A method of measuring cardiac output in a subject using the apparatus of any of claims 33, 34 or 36 comprising: i. Measuring {dot over (V)}CO₂ and P_(ET)CO₂ in a first state ii. Changing {dot over (V)}CO₂ for a time less than or equal to a recirculation time to a new {dot over (V)}CO₂, designated as {dot over (V)}CO₂′ iii. Determining a new PETCO₂ at {dot over (V)}CO₂′ designated as P_(ET)CO₂′ wherein said PETCO₂′ is the steady state end tidal PCO₂ after a change in {dot over (V)}CO₂ to {dot over (V)}CO₂′, or if no steady state is reached, then it is the extrapolated steady state end tidal PCO₂ from the exponential rise in end tidal PCO₂ within the recirculation time. iv. Determining {dot over (Q)} using the Differential Fick relationship
 57. The method of claim 56 wherein {dot over (V)}CO₂ in the first state is measured using the method of claim
 48. 58. The method of claim 56 wherein {dot over (V)}CO₂ in the first state is measured using the method of claim
 51. 59. The method of claim 56 wherein {dot over (V)}CO₂ in the first state is measured using the method of claim
 54. 60. The method of claim 56 wherein the FGS flow during the first state is equal to the subject's {dot over (V)}_(A).
 61. The method of claim 56 wherein the FGS flow during the second state is less than the subject's {dot over (V)}_(A).
 62. The method of claim 60 or 61 wherein the {dot over (V)}_(A) is determined according to the method of claim
 45. 63. The method of claim 60 or 61 wherein the {dot over (V)}_(A) is determined according to the method of claim
 46. 64. The method of claim 60 or 61 wherein the {dot over (V)}_(A) is determined according to the method of claim
 47. 65. The method of claim 56 wherein the {dot over (V)}CO₂is changed to {dot over (V)}CO₂′ by changing the concentration of CO₂ in FGS.
 66. The method of claim 56 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 67. The method of claim 57 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 68. The method of claim 58 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 69. The method of claim 59 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 70. The method of claim 60 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 71. The method of claim 61 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 72. The method of claim 62 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 73. The method of claim 63 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 74. The method of claim 64 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 75. The method of claim 65 wherein {dot over (V)}CO₂′ is determined as F_(ET)CO₂′×FGS flow, where F_(ET)CO₂′ is the end tidal CO₂ of the subject either at equilibrium or as extrapolated to equilibrium from the exponential rise in end tidal CO₂ values.
 76. A method of measuring cardiac output in a subject using the apparatus of any of claims 33, 34 or 36 comprising: i. Estimating the subject's {dot over (V)}_(A) (denoted {dot over (V)}_(A) _(PRELIM) ) based on weight, height, temperature, and sex. ii. setting the FGS flow into the circuit at a rate greater than the subjects minute ventilation ( {dot over (V)}E) iii. for a time less than or equal to a recirculation time, changing FGS flow to a value {dot over (V)}A¹ which is below {dot over (V)}A _(PRELIM). iv. Calculating {dot over (V)}CO₂ ¹={dot over (V)}A¹×F_(ET)CO₂ ¹, whereby F_(ET)CO₂ ¹ is the fractional end tidal CO₂ concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO₂ as extrapolated from the exponential rise in end tidal CO₂ values within the recirculation time. v. setting the FGS flow into the circuit at a rate greater than {dot over (V)}E and waiting for a steady state P_(ET)CO₂ to be reached. vi. for a time less than or equal to a recirculation time, changing FGS flow to a value {dot over (V)}A² which is below {dot over (V)}A _(PRELIM) and not equal to {dot over (V)}A¹. vii. Calculating {dot over (V)}CO₂ ²={dot over (V)}A²×F_(ET)CO₂ ², whereby F_(ET)CO₂ ² is the fractional end tidal CO₂ concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO₂ as extrapolated from the exponential rise in end tidal CO₂ values within the recirculation time. viii. Determine P_(ET)CO₂ ¹ from F_(ET)CO₂ ¹×ambient pressure, and P_(ET)CO₂ ² from F_(ET)CO₂ ²×ambient pressure ix. Using the values of {dot over (V)}CO₂ ¹, {dot over (V)}CO₂ ², P_(ET)CO₂ ¹, and P_(ET)CO₂ ² in the Differential Fick equation to determine cardiac output
 77. The method of claim 56 or 76 whereby the P_(ET)CO₂ values in the Fick equation are replaced by the PaCO₂ using the Kim Rahn Farhi method to identify the P_(ET)CO₂-PaCO₂ gradient
 78. The method of determining P vCO₂-Oxy in a subject using the apparatus of any of claims 33, 34 or 36 comprising: i. Determining {dot over (V)}A according to any of the methods in claims method of claims 45, 46, or c ii. Setting the FGS flow in the circuit equal to {dot over (V)}A and measuring inspired concentration of CO₂ and P_(ET)CO₂ iii. For a series of breaths no longer than a recirculation time changing the CO₂ concentration in the FGS and measuring inspired concentration of CO₂ and P_(ET)CO₂ iv. Using the values of inspired and expired concentrations as described by Fisher to calculate P vCO₂-Oxy
 79. The method of claim 45 wherein the {dot over (V)}_(A) so determined is utilized to determine the {dot over (V)}O₂ as {dot over (V)}_(A)×[F₁O₂−F_(ET)O₂] during the steady state where F₁O₂ is the O₂ concentration in FGS.
 80. The method of claim 46 wherein the {dot over (V)}_(A) so determined is utilized to determine the {dot over (V)}O₂ as {dot over (V)}_(A)×[F₁O₂−F_(ET)O₂] during the steady state where F₁O₂ is the O₂ concentration in FGS.
 81. The method of claim 47 wherein the {dot over (V)}_(A) so determined is utilized to determine the {dot over (V)}O₂ as {dot over (V)}_(A)×[F₁O₂−F_(ET)O₂] during the steady state where F₁O₂ is the O₂ concentration in FGS.
 82. A method of identifying the minute ventilation ({dot over (V)}_(E)) using any breathing circuit wherein when the subject's minute ventilation exceeds a first gas set (FGS) flow into the circuit, the balance of his/her ventilation is supplied from a second gas set (SGS) comprising i. setting the FGS flow into the circuit at a rate greater than the subject's minute ventilation ( {dot over (V)}E) ii. progressively lowering the FGS flow into the circuit, either breath by breath or continuously, until the FGS reservoir bag in the breathing circuit first collapses. The FGS flow when the bag first collapses is determined to be {dot over (V)}E.
 83. A method of determining the anatomical dead space comprising a. Measuring {dot over (V)}_(A) using any of the methods of claims 45 b. Measuring {dot over (V)}E c. Measuring the respiratory rate d. Determining anatomical dead space=({dot over (V)}E−{dot over (V)}_(A))/respiratory rate
 84. A method of determining the anatomical dead space comprising a. Measuring {dot over (V)}_(A) using any of the methods of claims 46 b. Measuring {dot over (V)}E c. Measuring the respiratory rate d. Determining anatomical dead space=({dot over (V)}E−{dot over (V)}_(A))/respiratory rate
 85. A method of determining the anatomical dead space comprising a. Measuring {dot over (V)}_(A) using any of the methods of claims 47 b. Measuring {dot over (V)}E c. Measuring the respiratory rate d. Determining anatomical dead space=({dot over (V)}E−{dot over (V)}_(A))/respiratory rate
 86. The method of determining physiological parameters in a subject using the apparatus of claims 33, 34 or 36 wherein the Kim Rahn Farhi approach is used to determine i) P vCO₂-oxy ii) true P vCO₂ iii) PaCO₂ iv) {dot over (Q)} v) true P vCO₂ plus the information from a pulse oximeter to determine mixed venous hemoglobin O₂ saturation
 87. The method of determining physiological parameters in a subject using the apparatus of claim 33, 34 or 36 wherein the differential CO₂ Fick technique of Gedeon and Orr is utilized to determine any combination of i) Pv CO₂-oxy ii) {dot over (Q)} iii) {dot over (V)}CO₂ iv) {dot over (V)}CO₂′ v) PETCO₂-PaCO₂ gradient determined using the PaCO₂ as determined by the Kim Rahn Farhi method from data collected while reducing the {dot over (V)}CO₂ in order to perform the differential Fick method.
 88. An improved method for determining {dot over (Q)}, {dot over (V)}_(A), {dot over (V)}CO₂, PvCO₂-oxy, true PvCO₂, PaCO₂, pulmonary shunt, anatomical dead space, and O₂ saturation in mixed venous blood in a subject breathing on any breathing circuit wherein when the subject's minute ventilation exceeds a first gas set (FGS) flow into the circuit, the balance of his/her ventilation is supplied from a second gas set (SGS) comprising i) setting the flow of FGS to the circuit to create two sets of data for said determination utilizing the Fick equations; (or) ii) determining the P_(ET)CO₂-PaCO₂ gradient from two independently derived values in the same subject; (or) iii) utilizing the Kim-Rahn-Farhi technique a series of reduced FGS flows simulates complete or partial breath holding, wherein the P_(ET)CO₂ of each breath is equivalent to a sequential alveolar sample;
 89. The method of 33, 34 or 36 used to measure {dot over (Q)} wherein {dot over (Q)} is used to determine SvO₂ using the relationship SvO₂=SaO₂−{dot over (V)}O₂/[Hb×CC×{dot over (Q)}], where Hb is haemoglobin, and CC (in ml O₂/gm Hb) is the capacity of haemoglobin to carry oxygen.
 90. The method or apparatus of claim 89 wherein the arterial O₂ hemoglobin saturation, is utilized with the O₂ saturation value in the pulmonary artery to calculate the fraction of shunted blood (assuming fully oxygenated blood in the end pulmonary capillary) thereof.
 91. The method or apparatus of claim 90 utilized to determine the fraction of shunted blood {dot over (Q)}_(S), which in conjunction with determination of cardiac output {dot over (Q)}_(T) may be used to determine {dot over (Q)}_(P) the pulmonary output via the relationship {dot over (Q)}_(T)={dot over (Q)}_(P)+{dot over (Q)}_(S)
 92. The method of claim 33, 34 or 36 wherein the O₂ saturation of haemoglobin in mixed venous blood, as determined therewith, is utilized to reveal a condition in a patient such as septic shock, or heart failure.
 93. The method of claims 44, 45, 47, 51, 53, 56, 82, 83, 84, 85, 88 which is automated by gauges, controls, and computer assisted devices in conjunction with at least one computer in order to control, activate and measure the variables and determinates thereof.
 94. The Method of claims 44, 45, 47, 51, 53, 56, 82, 83, 84, 85, 88 which is automated with at least one computing device. 